<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2022 Workiva-->
<!--r:845060b2-4e37-482c-8ae9-0e23a5d9619a,g:0f1463a6-505b-4611-9f37-25c6b798c5c1-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.caladrius.com/role/ConsolidatedStatementsofEquity" xlink:type="simple" xlink:href="clbs-20211231.xsd#ConsolidatedStatementsofEquity"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/ConsolidatedStatementsofEquity" xlink:type="extended" id="i4a846d916c134b2eb5a80f884198d611_ConsolidatedStatementsofEquity">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_05af0079-e9ff-4825-968b-23654e55c428" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_05af0079-e9ff-4825-968b-23654e55c428" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_0187dc07-0ab6-457c-86c9-25c80ed39de2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_SharesOutstanding_0187dc07-0ab6-457c-86c9-25c80ed39de2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_3277ebd2-8cf7-45f1-b211-a41c15855ea1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_3277ebd2-8cf7-45f1-b211-a41c15855ea1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_e9ab9180-2652-4b47-9ea2-a68ca1374692" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProfitLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_ProfitLoss_e9ab9180-2652-4b47-9ea2-a68ca1374692" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_23ef7a3f-0f71-4bd0-a316-8b311d74589a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_23ef7a3f-0f71-4bd0-a316-8b311d74589a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_1209cc5d-ed41-4452-b238-b47d806ba8ae" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_1209cc5d-ed41-4452-b238-b47d806ba8ae" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_b0a7d9c4-dc30-487f-9305-3ca07f38a71b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_b0a7d9c4-dc30-487f-9305-3ca07f38a71b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_eedd5569-c6d6-4306-892a-180d6aff7306" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_eedd5569-c6d6-4306-892a-180d6aff7306" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_a0c9804d-5791-4577-8e32-07471f6cd717" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_a0c9804d-5791-4577-8e32-07471f6cd717" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_c8adae18-9920-4e6b-9763-5ec5a74b9020" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_c8adae18-9920-4e6b-9763-5ec5a74b9020" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_2c5c5ad7-00a4-4449-a24a-97ae2d87584b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_25e5c586-d454-4891-b279-5464552f3e0d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_2c5c5ad7-00a4-4449-a24a-97ae2d87584b" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_e874aec8-9852-4832-8d45-eb5a01aa5a86" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_b1c31a53-61de-4972-81cf-bf8d3c7207ef" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_c0ec2df1-a39d-4ed8-af41-4f637ae392a4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_05af0079-e9ff-4825-968b-23654e55c428" xlink:to="loc_us-gaap_StatementTable_c0ec2df1-a39d-4ed8-af41-4f637ae392a4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_53f53346-5fcf-4799-9bcc-e48e992855c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_c0ec2df1-a39d-4ed8-af41-4f637ae392a4" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_53f53346-5fcf-4799-9bcc-e48e992855c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_53f53346-5fcf-4799-9bcc-e48e992855c5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_53f53346-5fcf-4799-9bcc-e48e992855c5" xlink:to="loc_us-gaap_EquityComponentDomain_53f53346-5fcf-4799-9bcc-e48e992855c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_2ae2690d-cf5b-4f31-9b84-550be0168fb0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_53f53346-5fcf-4799-9bcc-e48e992855c5" xlink:to="loc_us-gaap_EquityComponentDomain_2ae2690d-cf5b-4f31-9b84-550be0168fb0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ParentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_2ae2690d-cf5b-4f31-9b84-550be0168fb0" xlink:to="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockMember_866a01d2-98e9-4ff2-a079-be4349ea9037" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_PreferredStockMember_866a01d2-98e9-4ff2-a079-be4349ea9037" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_9cb01ae7-1a40-4a57-a87e-ed899a431e50" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_CommonStockMember_9cb01ae7-1a40-4a57-a87e-ed899a431e50" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_ec16d31f-2a55-45e5-bb10-aadefce204cc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_ec16d31f-2a55-45e5-bb10-aadefce204cc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_2d192b7b-f84c-4025-a454-acad5c92b164" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_2d192b7b-f84c-4025-a454-acad5c92b164" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_b37e7740-4a18-49fe-a784-392c140e24bc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_RetainedEarningsMember_b37e7740-4a18-49fe-a784-392c140e24bc" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockMember_80a79514-7559-4b01-b495-dcc1adf2a1ee" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TreasuryStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ParentMember_81234089-dd7f-4052-9558-cd3fb5f2e243" xlink:to="loc_us-gaap_TreasuryStockMember_80a79514-7559-4b01-b495-dcc1adf2a1ee" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncontrollingInterestMember_d35845a1-4bd1-46d1-af0c-8f570581857b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NoncontrollingInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_2ae2690d-cf5b-4f31-9b84-550be0168fb0" xlink:to="loc_us-gaap_NoncontrollingInterestMember_d35845a1-4bd1-46d1-af0c-8f570581857b" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/TheBusinessDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#TheBusinessDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/TheBusinessDetails" xlink:type="extended" id="if9ec0a56f4e14d3298291757aee99268_TheBusinessDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_9b374caf-bd86-4627-8dce-2e9e3d6208ee" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrantsReceivable_970225f3-203c-40d8-bf81-caa0cca07e0b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GrantsReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_9b374caf-bd86-4627-8dce-2e9e3d6208ee" xlink:to="loc_us-gaap_GrantsReceivable_970225f3-203c-40d8-bf81-caa0cca07e0b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_b97ab80e-fc6d-47bf-93a6-62c64050baf4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_9b374caf-bd86-4627-8dce-2e9e3d6208ee" xlink:to="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_b97ab80e-fc6d-47bf-93a6-62c64050baf4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_1c5f5af4-1ab9-47dd-a107-1803fc88c02a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_b97ab80e-fc6d-47bf-93a6-62c64050baf4" xlink:to="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_1c5f5af4-1ab9-47dd-a107-1803fc88c02a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProjectMember_1c5f5af4-1ab9-47dd-a107-1803fc88c02a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProjectMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_1c5f5af4-1ab9-47dd-a107-1803fc88c02a" xlink:to="loc_us-gaap_ProjectMember_1c5f5af4-1ab9-47dd-a107-1803fc88c02a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProjectMember_e463e2ad-1594-47dc-b919-bdc006d730d7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProjectMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CapitalizedCostsOfUnprovedPropertiesExcludedFromAmortizationByPropertyOrProjectAxis_1c5f5af4-1ab9-47dd-a107-1803fc88c02a" xlink:to="loc_us-gaap_ProjectMember_e463e2ad-1594-47dc-b919-bdc006d730d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_CLBS16TreatmentOfCMDMember_e16ca443-33b4-4fad-b52f-e3e5b0f54838" xlink:href="clbs-20211231.xsd#clbs_CLBS16TreatmentOfCMDMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProjectMember_e463e2ad-1594-47dc-b919-bdc006d730d7" xlink:to="loc_clbs_CLBS16TreatmentOfCMDMember_e16ca443-33b4-4fad-b52f-e3e5b0f54838" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#SummaryofSignificantAccountingPoliciesDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/SummaryofSignificantAccountingPoliciesDetails" xlink:type="extended" id="iaa828cdb416142278ffde8a8b0cf2768_SummaryofSignificantAccountingPoliciesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_24e32422-779e-495d-96e9-fa8358378719" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_6d41b536-ef72-41fb-bd78-7fcf8864a314" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_24e32422-779e-495d-96e9-fa8358378719" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_6d41b536-ef72-41fb-bd78-7fcf8864a314" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a190e933-8106-4d2d-812b-68b478ed699b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_24e32422-779e-495d-96e9-fa8358378719" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a190e933-8106-4d2d-812b-68b478ed699b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bef6879f-4809-49f0-a0eb-16bade456d62" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a190e933-8106-4d2d-812b-68b478ed699b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bef6879f-4809-49f0-a0eb-16bade456d62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_bef6879f-4809-49f0-a0eb-16bade456d62_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bef6879f-4809-49f0-a0eb-16bade456d62" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_bef6879f-4809-49f0-a0eb-16bade456d62_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_37e81acc-ff8a-4d88-b801-3d6b425cf815" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bef6879f-4809-49f0-a0eb-16bade456d62" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_37e81acc-ff8a-4d88-b801-3d6b425cf815" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_d9eea33c-1780-441e-8132-8c1926c8b84c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_37e81acc-ff8a-4d88-b801-3d6b425cf815" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_d9eea33c-1780-441e-8132-8c1926c8b84c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_d831a233-0261-4425-8d31-3afb582fc139" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_37e81acc-ff8a-4d88-b801-3d6b425cf815" xlink:to="loc_us-gaap_ComputerEquipmentMember_d831a233-0261-4425-8d31-3afb582fc139" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_f85fc976-a482-40a6-9ceb-08c7233df711" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_37e81acc-ff8a-4d88-b801-3d6b425cf815" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_f85fc976-a482-40a6-9ceb-08c7233df711" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/AvailableforSaleSecuritiesSummaryDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#AvailableforSaleSecuritiesSummaryDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/AvailableforSaleSecuritiesSummaryDetails" xlink:type="extended" id="i1484d9edfb794bd8b81070a9beb6237a_AvailableforSaleSecuritiesSummaryDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_00cf49b3-a722-4a7e-8d6b-80de852f2f70" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_00cf49b3-a722-4a7e-8d6b-80de852f2f70" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_086e2a28-d417-4bea-aa55-e9eac04f6c47" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_086e2a28-d417-4bea-aa55-e9eac04f6c47" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_201f901e-ff76-428d-b35c-32cf2ac5254a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_201f901e-ff76-428d-b35c-32cf2ac5254a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_3ee50742-c423-46eb-8c39-82b6707f1039" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_3ee50742-c423-46eb-8c39-82b6707f1039" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_0e0f3b48-47c7-430c-9689-edcabd57cd76" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_8c8a7227-e004-4800-aa48-2f8f60243ac4" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_0e0f3b48-47c7-430c-9689-edcabd57cd76" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_24039a3c-938c-417a-8704-1f77a027051f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_0e0f3b48-47c7-430c-9689-edcabd57cd76" xlink:to="loc_us-gaap_FinancialInstrumentAxis_24039a3c-938c-417a-8704-1f77a027051f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_24039a3c-938c-417a-8704-1f77a027051f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_24039a3c-938c-417a-8704-1f77a027051f" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_24039a3c-938c-417a-8704-1f77a027051f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74ed7212-efdd-4801-94c5-61ea5d935b45" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_24039a3c-938c-417a-8704-1f77a027051f" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74ed7212-efdd-4801-94c5-61ea5d935b45" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_6f175543-f892-4dd1-9966-e7fcd2063f51" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74ed7212-efdd-4801-94c5-61ea5d935b45" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_6f175543-f892-4dd1-9966-e7fcd2063f51" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_cfcf37c7-74fa-4ddd-a6ce-a0694e8777c2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74ed7212-efdd-4801-94c5-61ea5d935b45" xlink:to="loc_us-gaap_MoneyMarketFundsMember_cfcf37c7-74fa-4ddd-a6ce-a0694e8777c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USStatesAndPoliticalSubdivisionsMember_1a7a49d9-c35f-4f4d-b25b-be166afa6a5f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_74ed7212-efdd-4801-94c5-61ea5d935b45" xlink:to="loc_us-gaap_USStatesAndPoliticalSubdivisionsMember_1a7a49d9-c35f-4f4d-b25b-be166afa6a5f" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/AvailableforSaleSecuritiesClassificationonConsolidatedBalanceSheetsDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#AvailableforSaleSecuritiesClassificationonConsolidatedBalanceSheetsDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/AvailableforSaleSecuritiesClassificationonConsolidatedBalanceSheetsDetails" xlink:type="extended" id="i4e3631ba312449359527fd44c592b547_AvailableforSaleSecuritiesClassificationonConsolidatedBalanceSheetsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dc3d271b-369a-4bd6-9821-7ce6dd44c8f5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_57addc31-1bbc-4447-9f68-51c631a4ece6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dc3d271b-369a-4bd6-9821-7ce6dd44c8f5" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_57addc31-1bbc-4447-9f68-51c631a4ece6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_bb934fb8-a714-49a7-a227-cbcf89d60ebe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dc3d271b-369a-4bd6-9821-7ce6dd44c8f5" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_bb934fb8-a714-49a7-a227-cbcf89d60ebe" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationAxis_3bf535cb-9b3a-4b68-8707-b23270a67d42" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_bb934fb8-a714-49a7-a227-cbcf89d60ebe" xlink:to="loc_us-gaap_BalanceSheetLocationAxis_3bf535cb-9b3a-4b68-8707-b23270a67d42" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_3bf535cb-9b3a-4b68-8707-b23270a67d42_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_3bf535cb-9b3a-4b68-8707-b23270a67d42" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_3bf535cb-9b3a-4b68-8707-b23270a67d42_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BalanceSheetLocationDomain_870139c7-d514-4908-af31-bf2baa3b9e2f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BalanceSheetLocationAxis_3bf535cb-9b3a-4b68-8707-b23270a67d42" xlink:to="loc_us-gaap_BalanceSheetLocationDomain_870139c7-d514-4908-af31-bf2baa3b9e2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsMember_66eaf030-4b6e-438f-8a07-0029bff635c0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_870139c7-d514-4908-af31-bf2baa3b9e2f" xlink:to="loc_us-gaap_CashAndCashEquivalentsMember_66eaf030-4b6e-438f-8a07-0029bff635c0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_MarketableSecuritiesMember_64610be8-77b6-4f26-8f68-a3b102ba9c1e" xlink:href="clbs-20211231.xsd#clbs_MarketableSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BalanceSheetLocationDomain_870139c7-d514-4908-af31-bf2baa3b9e2f" xlink:to="loc_clbs_MarketableSecuritiesMember_64610be8-77b6-4f26-8f68-a3b102ba9c1e" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/PropertyandEquipmentSummaryDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#PropertyandEquipmentSummaryDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/PropertyandEquipmentSummaryDetails" xlink:type="extended" id="i0bbc9950833a4040a6cce419e61532b9_PropertyandEquipmentSummaryDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_64971296-deed-4f77-b6e7-351eebee7620" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_5df0510c-4c77-4afe-a53d-cc700d7e6356" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_64971296-deed-4f77-b6e7-351eebee7620" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_5df0510c-4c77-4afe-a53d-cc700d7e6356" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_367edbf8-b676-4c03-81be-9c60807eb08e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_64971296-deed-4f77-b6e7-351eebee7620" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_367edbf8-b676-4c03-81be-9c60807eb08e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_8d40343d-4759-4cc5-9045-87a2032d7b3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_64971296-deed-4f77-b6e7-351eebee7620" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_8d40343d-4759-4cc5-9045-87a2032d7b3e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fbcddba6-677d-46dd-8abc-9db055af4dc4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_64971296-deed-4f77-b6e7-351eebee7620" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fbcddba6-677d-46dd-8abc-9db055af4dc4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_fbcddba6-677d-46dd-8abc-9db055af4dc4" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ee862a01-8eaa-4d29-ab6f-de8bd29b0d41" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_19ff6e96-525f-43d0-9c8b-c5c1eac6adf3" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ee862a01-8eaa-4d29-ab6f-de8bd29b0d41" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_5e737a79-a5f7-47bd-b374-d608655d7019" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ee862a01-8eaa-4d29-ab6f-de8bd29b0d41" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_5e737a79-a5f7-47bd-b374-d608655d7019" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_11e70072-f36e-4de2-94c8-fcdf433de8e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ee862a01-8eaa-4d29-ab6f-de8bd29b0d41" xlink:to="loc_us-gaap_ComputerEquipmentMember_11e70072-f36e-4de2-94c8-fcdf433de8e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_d0a5a0a3-7b8b-41ba-bf25-c9a2c98ea79f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_ee862a01-8eaa-4d29-ab6f-de8bd29b0d41" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_d0a5a0a3-7b8b-41ba-bf25-c9a2c98ea79f" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/LossPerShareDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#LossPerShareDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/LossPerShareDetails" xlink:type="extended" id="id6173af6f2694cd684033bcb48440116_LossPerShareDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a03c7d9c-6315-419e-ab00-cd25411f52c2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_77db4e62-e4ad-4908-a680-c133b9ec16e2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a03c7d9c-6315-419e-ab00-cd25411f52c2" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_77db4e62-e4ad-4908-a680-c133b9ec16e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0f72c2d-0a68-4a0b-86d7-2948cb34f818" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a03c7d9c-6315-419e-ab00-cd25411f52c2" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0f72c2d-0a68-4a0b-86d7-2948cb34f818" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_edf8cc13-b962-46a0-8472-bbaa4b063e60" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_b0f72c2d-0a68-4a0b-86d7-2948cb34f818" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_edf8cc13-b962-46a0-8472-bbaa4b063e60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_edf8cc13-b962-46a0-8472-bbaa4b063e60_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_edf8cc13-b962-46a0-8472-bbaa4b063e60" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_edf8cc13-b962-46a0-8472-bbaa4b063e60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_da8130f6-be40-4f1e-b518-2cc510857c3e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_edf8cc13-b962-46a0-8472-bbaa4b063e60" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_da8130f6-be40-4f1e-b518-2cc510857c3e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_f33c2fd0-e7dc-4910-9469-d672fd03090c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_da8130f6-be40-4f1e-b518-2cc510857c3e" xlink:to="loc_us-gaap_EmployeeStockOptionMember_f33c2fd0-e7dc-4910-9469-d672fd03090c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_221ea354-3302-4a7d-bf99-384a420d2e78" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_da8130f6-be40-4f1e-b518-2cc510857c3e" xlink:to="loc_us-gaap_WarrantMember_221ea354-3302-4a7d-bf99-384a420d2e78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_3ccd6acd-8b05-49fa-acf1-5331ce18e09f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_da8130f6-be40-4f1e-b518-2cc510857c3e" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_3ccd6acd-8b05-49fa-acf1-5331ce18e09f" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#FairValueMeasurementsDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/FairValueMeasurementsDetails" xlink:type="extended" id="if3299338073f40b79b1bf55547bbd569_FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_c4295414-10f4-4fb7-87b4-8ed33ff38d48" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_c67ea93a-b0f8-47fb-9dd2-405ebc7bd6a1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_c4295414-10f4-4fb7-87b4-8ed33ff38d48" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_c67ea93a-b0f8-47fb-9dd2-405ebc7bd6a1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_04be93bd-b2ac-4652-a411-1fe86a591a36" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_c67ea93a-b0f8-47fb-9dd2-405ebc7bd6a1" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_04be93bd-b2ac-4652-a411-1fe86a591a36" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_1a6d8f7a-3e9e-4556-a641-7cc0ba0df4c3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_c67ea93a-b0f8-47fb-9dd2-405ebc7bd6a1" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_1a6d8f7a-3e9e-4556-a641-7cc0ba0df4c3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_83b7bfbb-68dd-4ed4-8d06-88aad0180716" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_c4295414-10f4-4fb7-87b4-8ed33ff38d48" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_83b7bfbb-68dd-4ed4-8d06-88aad0180716" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_5499ddef-89d8-4976-b3b3-9246e58eb431" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_83b7bfbb-68dd-4ed4-8d06-88aad0180716" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_5499ddef-89d8-4976-b3b3-9246e58eb431" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_5499ddef-89d8-4976-b3b3-9246e58eb431_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_5499ddef-89d8-4976-b3b3-9246e58eb431" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_5499ddef-89d8-4976-b3b3-9246e58eb431_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_6bd10ac5-375c-451b-b19a-66505a5a31c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_5499ddef-89d8-4976-b3b3-9246e58eb431" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_6bd10ac5-375c-451b-b19a-66505a5a31c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_fd159745-5b5f-4f0a-ba8a-98ecdcc4851d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_6bd10ac5-375c-451b-b19a-66505a5a31c5" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_fd159745-5b5f-4f0a-ba8a-98ecdcc4851d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_09f56641-de66-4eb0-b347-db0dd9c074e5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_83b7bfbb-68dd-4ed4-8d06-88aad0180716" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_09f56641-de66-4eb0-b347-db0dd9c074e5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_09f56641-de66-4eb0-b347-db0dd9c074e5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_09f56641-de66-4eb0-b347-db0dd9c074e5" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_09f56641-de66-4eb0-b347-db0dd9c074e5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7755dd55-c9b6-41f4-a4e3-f765a0a14dca" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_09f56641-de66-4eb0-b347-db0dd9c074e5" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7755dd55-c9b6-41f4-a4e3-f765a0a14dca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_1af238fe-20d8-44de-a1c5-ed42e87d0617" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7755dd55-c9b6-41f4-a4e3-f765a0a14dca" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_1af238fe-20d8-44de-a1c5-ed42e87d0617" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_fd30bd8b-91e7-4711-831e-6a7d81620891" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7755dd55-c9b6-41f4-a4e3-f765a0a14dca" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_fd30bd8b-91e7-4711-831e-6a7d81620891" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_e58259df-7edc-4b08-b785-296fd419b1c0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_7755dd55-c9b6-41f4-a4e3-f765a0a14dca" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_e58259df-7edc-4b08-b785-296fd419b1c0" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/StockholdersEquityEquityPlanDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#StockholdersEquityEquityPlanDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/StockholdersEquityEquityPlanDetails" xlink:type="extended" id="i337ffce93a9948689929650ba7e4218b_StockholdersEquityEquityPlanDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_4862b2d0-1f0d-47cb-9c12-9eb8e85ccf21" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_4862b2d0-1f0d-47cb-9c12-9eb8e85ccf21" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_9e5fa60c-cddb-41b8-bfdf-69f4383a38f2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_9e5fa60c-cddb-41b8-bfdf-69f4383a38f2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_b3fd1b9e-a506-47c3-a5d2-2930b9cf86d6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_b3fd1b9e-a506-47c3-a5d2-2930b9cf86d6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_NumberofOfferingPeriodsEmployeeStockPurchasePlan_df64cbc2-5e45-405d-8a37-a67ad77eff13" xlink:href="clbs-20211231.xsd#clbs_NumberofOfferingPeriodsEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_NumberofOfferingPeriodsEmployeeStockPurchasePlan_df64cbc2-5e45-405d-8a37-a67ad77eff13" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_OfferingPeriodsEmployeeStockPurchasePlanTerm_b3d4c7ac-9f5b-491e-a299-2e5581a68167" xlink:href="clbs-20211231.xsd#clbs_OfferingPeriodsEmployeeStockPurchasePlanTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_OfferingPeriodsEmployeeStockPurchasePlanTerm_b3d4c7ac-9f5b-491e-a299-2e5581a68167" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployeePercent_c8973c93-a320-4775-8ef7-fd1cb07c8978" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployeePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployeePercent_c8973c93-a320-4775-8ef7-fd1cb07c8978" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployee_729a2219-d868-4197-8216-e86b54675812" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_EmployeeStockPurchasePlanMaximumAnnualContributionPerEmployee_729a2219-d868-4197-8216-e86b54675812" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnEnrollmentDate_5b2099d0-877f-4b1b-ae16-6dd5234d265e" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnEnrollmentDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnEnrollmentDate_5b2099d0-877f-4b1b-ae16-6dd5234d265e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnExerciseDate_1887ec9f-f9a7-4cdd-8e0f-82cb34cc594f" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnExerciseDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_clbs_EmployeeStockPurchasePlanPurchasePricePercentOfClosingPriceOnExerciseDate_1887ec9f-f9a7-4cdd-8e0f-82cb34cc594f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_ef9a7156-618a-4a6e-b49f-bea434020367" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_ef9a7156-618a-4a6e-b49f-bea434020367" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7ee6e889-5833-45ef-8da7-6bb69861d649" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9462f4ef-75e0-4acf-8a18-3a2302e6d086" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7ee6e889-5833-45ef-8da7-6bb69861d649" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_3d2532f1-a729-44a1-8d93-86abb58de0dd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7ee6e889-5833-45ef-8da7-6bb69861d649" xlink:to="loc_us-gaap_PlanNameAxis_3d2532f1-a729-44a1-8d93-86abb58de0dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_3d2532f1-a729-44a1-8d93-86abb58de0dd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_3d2532f1-a729-44a1-8d93-86abb58de0dd" xlink:to="loc_us-gaap_PlanNameDomain_3d2532f1-a729-44a1-8d93-86abb58de0dd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_3d2532f1-a729-44a1-8d93-86abb58de0dd" xlink:to="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EquityIncentiveCompensationPlan2018Member_5cb4212c-0417-4981-84a9-154aaab8a983" xlink:href="clbs-20211231.xsd#clbs_EquityIncentiveCompensationPlan2018Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:to="loc_clbs_EquityIncentiveCompensationPlan2018Member_5cb4212c-0417-4981-84a9-154aaab8a983" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlanMember_fabd725d-fa34-4da0-abab-3d5c7be39adc" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:to="loc_clbs_EmployeeStockPurchasePlanMember_fabd725d-fa34-4da0-abab-3d5c7be39adc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlan2012Member_8c148aa5-fe1d-44b6-b734-303b097e548d" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlan2012Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:to="loc_clbs_EmployeeStockPurchasePlan2012Member_8c148aa5-fe1d-44b6-b734-303b097e548d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlan2017Member_df158b66-e03c-4cb6-92e3-e15190e42bd3" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlan2017Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:to="loc_clbs_EmployeeStockPurchasePlan2017Member_df158b66-e03c-4cb6-92e3-e15190e42bd3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_EmployeeStockPurchasePlan2017AmendedMember_f5aa8d55-53e6-436f-9978-f2b7e4865dc9" xlink:href="clbs-20211231.xsd#clbs_EmployeeStockPurchasePlan2017AmendedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_ffb171b9-e1ca-48a2-bf32-7029cac71a1e" xlink:to="loc_clbs_EmployeeStockPurchasePlan2017AmendedMember_f5aa8d55-53e6-436f-9978-f2b7e4865dc9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_4bd6a4c2-33a4-4b78-8005-1b084f6afff9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7ee6e889-5833-45ef-8da7-6bb69861d649" xlink:to="loc_us-gaap_AwardTypeAxis_4bd6a4c2-33a4-4b78-8005-1b084f6afff9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_4bd6a4c2-33a4-4b78-8005-1b084f6afff9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_4bd6a4c2-33a4-4b78-8005-1b084f6afff9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_4bd6a4c2-33a4-4b78-8005-1b084f6afff9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_72b7d393-5b3c-48ca-83a9-727fa6eb50e3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_4bd6a4c2-33a4-4b78-8005-1b084f6afff9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_72b7d393-5b3c-48ca-83a9-727fa6eb50e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_903e90c1-0672-4595-9a1d-c8be6f82f74f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_72b7d393-5b3c-48ca-83a9-727fa6eb50e3" xlink:to="loc_us-gaap_EmployeeStockOptionMember_903e90c1-0672-4595-9a1d-c8be6f82f74f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingAxis_694f55ba-006c-40b2-a1e8-273e324ca06b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7ee6e889-5833-45ef-8da7-6bb69861d649" xlink:to="loc_us-gaap_VestingAxis_694f55ba-006c-40b2-a1e8-273e324ca06b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_694f55ba-006c-40b2-a1e8-273e324ca06b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VestingAxis_694f55ba-006c-40b2-a1e8-273e324ca06b" xlink:to="loc_us-gaap_VestingDomain_694f55ba-006c-40b2-a1e8-273e324ca06b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_386dc372-e7c7-4c11-a419-26221c7359d9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VestingAxis_694f55ba-006c-40b2-a1e8-273e324ca06b" xlink:to="loc_us-gaap_VestingDomain_386dc372-e7c7-4c11-a419-26221c7359d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_20b9ea79-b763-44c9-acea-44d42f5cc60f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_386dc372-e7c7-4c11-a419-26221c7359d9" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_20b9ea79-b763-44c9-acea-44d42f5cc60f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheTwoMember_45961a7c-55b2-413b-a18c-1214bacc1e55" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_386dc372-e7c7-4c11-a419-26221c7359d9" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheTwoMember_45961a7c-55b2-413b-a18c-1214bacc1e55" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheThreeMember_0565eb0f-6e27-4cb9-9d5e-58be32dba5e8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheThreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_386dc372-e7c7-4c11-a419-26221c7359d9" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheThreeMember_0565eb0f-6e27-4cb9-9d5e-58be32dba5e8" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/StockholdersEquityEquityIssuancesDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#StockholdersEquityEquityIssuancesDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/StockholdersEquityEquityIssuancesDetails" xlink:type="extended" id="i56f1afb094714de2bfb98b1f96857146_StockholdersEquityEquityIssuancesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockAggregateOfferingAmountAuthorizedPerAgreement_2f47b314-21b1-4db8-9344-b54d9929ef95" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockAggregateOfferingAmountAuthorizedPerAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockAggregateOfferingAmountAuthorizedPerAgreement_2f47b314-21b1-4db8-9344-b54d9929ef95" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_StockIssuedDuringPeriodSharesIssuedAsConsideration_89028d77-7d82-45e0-9926-d19f6ce02226" xlink:href="clbs-20211231.xsd#clbs_StockIssuedDuringPeriodSharesIssuedAsConsideration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_StockIssuedDuringPeriodSharesIssuedAsConsideration_89028d77-7d82-45e0-9926-d19f6ce02226" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_fa5c463d-4c04-4376-9a73-7caca6b27c18" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_fa5c463d-4c04-4376-9a73-7caca6b27c18" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_853d04b5-0847-47a2-ab72-e2504f76dd6e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_853d04b5-0847-47a2-ab72-e2504f76dd6e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_6593c21e-9a13-433a-b370-82299a2d593e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_6593c21e-9a13-433a-b370-82299a2d593e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_TermOfAgreement_86b7689b-dabe-4191-a48e-39238e170b55" xlink:href="clbs-20211231.xsd#clbs_TermOfAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_TermOfAgreement_86b7689b-dabe-4191-a48e-39238e170b55" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockAmountPerAgreementAllowableToDirectCounterpartyToPurchaseRegularPurchase_181cb76f-657f-4a12-911b-b4c755f0e1f0" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockAmountPerAgreementAllowableToDirectCounterpartyToPurchaseRegularPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockAmountPerAgreementAllowableToDirectCounterpartyToPurchaseRegularPurchase_181cb76f-657f-4a12-911b-b4c755f0e1f0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockMaximumAmountPerAgreementPerTransactionForDirectCounterpartyPurchaseRegularPurchase_7828fcba-a4d6-4d6f-8b88-d43877badbb3" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockMaximumAmountPerAgreementPerTransactionForDirectCounterpartyPurchaseRegularPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockMaximumAmountPerAgreementPerTransactionForDirectCounterpartyPurchaseRegularPurchase_7828fcba-a4d6-4d6f-8b88-d43877badbb3" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesInRegularPurchase_347a77c9-cb38-4058-8bc1-4a205d32df21" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesInRegularPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesInRegularPurchase_347a77c9-cb38-4058-8bc1-4a205d32df21" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesOfStockTradedDuringSpecifiedPeriod_38e712f3-418d-4704-8fcf-76f211872ee0" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesOfStockTradedDuringSpecifiedPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockMaximumSharesAllowedInAcceleratedPurchaseAsPercentOfSharesOfStockTradedDuringSpecifiedPeriod_38e712f3-418d-4704-8fcf-76f211872ee0" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_RegistrationRightsAgreementMaximumBeneficialOwnershipAllowableForCounterparty_8fc53f47-9911-42fc-bb0d-4b6fc9c964a7" xlink:href="clbs-20211231.xsd#clbs_RegistrationRightsAgreementMaximumBeneficialOwnershipAllowableForCounterparty"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_RegistrationRightsAgreementMaximumBeneficialOwnershipAllowableForCounterparty_8fc53f47-9911-42fc-bb0d-4b6fc9c964a7" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_PurchaseAgreementAcceleratedPurchaseSpecifiedStockFloorPrice_826de393-2dd9-4f98-a2f1-62d12eb873b8" xlink:href="clbs-20211231.xsd#clbs_PurchaseAgreementAcceleratedPurchaseSpecifiedStockFloorPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_PurchaseAgreementAcceleratedPurchaseSpecifiedStockFloorPrice_826de393-2dd9-4f98-a2f1-62d12eb873b8" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_SaleOfStockCommissionOnGrossProceedsDueToThirdPartyUponPercent_c05c4ab9-d5d8-46b4-ad0b-c30b9d891b5e" xlink:href="clbs-20211231.xsd#clbs_SaleOfStockCommissionOnGrossProceedsDueToThirdPartyUponPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_clbs_SaleOfStockCommissionOnGrossProceedsDueToThirdPartyUponPercent_c05c4ab9-d5d8-46b4-ad0b-c30b9d891b5e" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_150a58e9-d0ae-426e-a810-4656ea0edb96" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_150a58e9-d0ae-426e-a810-4656ea0edb96" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_f1b05989-51a5-40f0-8030-d73daa9ce042" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_f1b05989-51a5-40f0-8030-d73daa9ce042" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_63f0fddd-ef59-457a-b3c8-f3ed155fa90e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_63f0fddd-ef59-457a-b3c8-f3ed155fa90e" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_21136483-ebac-4b53-a613-4948526eaf19" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_21136483-ebac-4b53-a613-4948526eaf19" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingTerm_572411e6-88ea-4004-b3bb-971809928ed3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WarrantsAndRightsOutstandingTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingTerm_572411e6-88ea-4004-b3bb-971809928ed3" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight_2b719106-c0d9-407f-a7e5-b2efff509a4e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByEachWarrantOrRight_2b719106-c0d9-407f-a7e5-b2efff509a4e" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesOther_4ed5dcdb-9eab-4adc-b9f7-1a68881e2c86" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesOther"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesOther_4ed5dcdb-9eab-4adc-b9f7-1a68881e2c86" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromWarrantExercises_8d305b7a-7ce6-40f8-bc54-c2b93f7edb4e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromWarrantExercises"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ProceedsFromWarrantExercises_8d305b7a-7ce6-40f8-bc54-c2b93f7edb4e" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_c76fadc7-f271-4cd9-b7e4-81d4b4d1b781" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_79bb43a1-3914-4401-9f27-c04f2c38d62f" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_c76fadc7-f271-4cd9-b7e4-81d4b4d1b781" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_c76fadc7-f271-4cd9-b7e4-81d4b4d1b781" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_4d18a83a-0ddc-445f-93fe-e419b2ee2f6d" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_LincolnParkAgreementMember_104893cc-3909-432a-82e7-3fa505c64b7f" xlink:href="clbs-20211231.xsd#clbs_LincolnParkAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_LincolnParkAgreementMember_104893cc-3909-432a-82e7-3fa505c64b7f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_H.C.WainwrightSalesAmendedAgreementMember_929c26ba-eafd-4a6d-96b3-126384b8f197" xlink:href="clbs-20211231.xsd#clbs_H.C.WainwrightSalesAmendedAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_H.C.WainwrightSalesAmendedAgreementMember_929c26ba-eafd-4a6d-96b3-126384b8f197" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_AtTheMarketOfferingAgreementMember_1d13037f-0ba4-4c10-8d34-961930c95a95" xlink:href="clbs-20211231.xsd#clbs_AtTheMarketOfferingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_AtTheMarketOfferingAgreementMember_1d13037f-0ba4-4c10-8d34-961930c95a95" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_InstitutionalPurchaseAgreementMember_1971059a-2dd1-4049-b7a5-2bba63c18c90" xlink:href="clbs-20211231.xsd#clbs_InstitutionalPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_InstitutionalPurchaseAgreementMember_1971059a-2dd1-4049-b7a5-2bba63c18c90" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_AdditionalPurchaseAgreementMember_358e1fd2-edbb-4098-a17b-86e98216e7fb" xlink:href="clbs-20211231.xsd#clbs_AdditionalPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_AdditionalPurchaseAgreementMember_358e1fd2-edbb-4098-a17b-86e98216e7fb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_January2021PurchaseAgreementMember_cd987d5e-cf69-458c-a7cd-5307b59085c7" xlink:href="clbs-20211231.xsd#clbs_January2021PurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_2a5cf593-7582-4644-b3a5-70b716a62533" xlink:to="loc_clbs_January2021PurchaseAgreementMember_cd987d5e-cf69-458c-a7cd-5307b59085c7" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/StockholdersEquityRestrictedStockandRestrictedStockUnitsDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#StockholdersEquityRestrictedStockandRestrictedStockUnitsDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/StockholdersEquityRestrictedStockandRestrictedStockUnitsDetails" xlink:type="extended" id="ia88497524bd64178b3984f46dc9ace01_StockholdersEquityRestrictedStockandRestrictedStockUnitsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9fc3bdf5-8062-4519-b8ce-a7d2b1ba6dc3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:href="clbs-20211231.xsd#clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9fc3bdf5-8062-4519-b8ce-a7d2b1ba6dc3" xlink:to="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_def7a308-9758-46dc-9757-25dcac0670f2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_def7a308-9758-46dc-9757-25dcac0670f2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_af1017d6-64be-4efa-ba1a-fbdd0df6f5d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_af1017d6-64be-4efa-ba1a-fbdd0df6f5d8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_d5c31100-1286-40de-b9b7-de9eb8867432" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_d5c31100-1286-40de-b9b7-de9eb8867432" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_61660bfa-6d79-423e-8799-a00cdaa57bd9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_clbs_RestrictedStockAndRestrictedStockUnitsIssuedAbstract_ee792d89-8393-4348-ba71-64868592d294" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_61660bfa-6d79-423e-8799-a00cdaa57bd9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_31f42d7e-007e-4b5a-9da1-16e8f4a72087" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9fc3bdf5-8062-4519-b8ce-a7d2b1ba6dc3" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_31f42d7e-007e-4b5a-9da1-16e8f4a72087" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_8dfec4b1-dbdc-4346-b400-ec8878bdd320" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_31f42d7e-007e-4b5a-9da1-16e8f4a72087" xlink:to="loc_us-gaap_AwardTypeAxis_8dfec4b1-dbdc-4346-b400-ec8878bdd320" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8dfec4b1-dbdc-4346-b400-ec8878bdd320_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_8dfec4b1-dbdc-4346-b400-ec8878bdd320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8dfec4b1-dbdc-4346-b400-ec8878bdd320_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2a54db4-e8a0-43c1-bd3f-bf096ad41605" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_8dfec4b1-dbdc-4346-b400-ec8878bdd320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2a54db4-e8a0-43c1-bd3f-bf096ad41605" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockMember_dd46870f-d8e5-48fb-8a35-ddfe81fdb7d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2a54db4-e8a0-43c1-bd3f-bf096ad41605" xlink:to="loc_us-gaap_RestrictedStockMember_dd46870f-d8e5-48fb-8a35-ddfe81fdb7d2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_30ad8883-b206-4709-8ed2-71f38c2c3b6a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2a54db4-e8a0-43c1-bd3f-bf096ad41605" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_30ad8883-b206-4709-8ed2-71f38c2c3b6a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_38378fa9-a72b-40a2-ab9e-d77c20f1a04a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_31f42d7e-007e-4b5a-9da1-16e8f4a72087" xlink:to="loc_srt_RangeAxis_38378fa9-a72b-40a2-ab9e-d77c20f1a04a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_38378fa9-a72b-40a2-ab9e-d77c20f1a04a_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_38378fa9-a72b-40a2-ab9e-d77c20f1a04a" xlink:to="loc_srt_RangeMember_38378fa9-a72b-40a2-ab9e-d77c20f1a04a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_64977f9d-9879-42a3-966a-4a1b8e82041d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_38378fa9-a72b-40a2-ab9e-d77c20f1a04a" xlink:to="loc_srt_RangeMember_64977f9d-9879-42a3-966a-4a1b8e82041d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_63219f01-1f4c-4c3c-ae67-84de08d73d8f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_64977f9d-9879-42a3-966a-4a1b8e82041d" xlink:to="loc_srt_MinimumMember_63219f01-1f4c-4c3c-ae67-84de08d73d8f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_9497345e-18f9-4ef0-bc60-54273dff9a53" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_64977f9d-9879-42a3-966a-4a1b8e82041d" xlink:to="loc_srt_MaximumMember_9497345e-18f9-4ef0-bc60-54273dff9a53" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/ShareBasedCompensationShareBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#ShareBasedCompensationShareBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/ShareBasedCompensationShareBasedCompensationExpenseDetails" xlink:type="extended" id="if1c44de9a887449bb5a2ef5d21880050_ShareBasedCompensationShareBasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_488a9e19-6444-4f92-a732-e3bf76f4d723" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_de5f79b3-5aee-4937-8526-43eece5925d5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_488a9e19-6444-4f92-a732-e3bf76f4d723" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_de5f79b3-5aee-4937-8526-43eece5925d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_bbac356a-478a-4ec7-b1db-87c1b24abe2d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_488a9e19-6444-4f92-a732-e3bf76f4d723" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_bbac356a-478a-4ec7-b1db-87c1b24abe2d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_94234faf-9aca-4e72-8712-4361532fa604" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_bbac356a-478a-4ec7-b1db-87c1b24abe2d" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_94234faf-9aca-4e72-8712-4361532fa604" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_94234faf-9aca-4e72-8712-4361532fa604_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_94234faf-9aca-4e72-8712-4361532fa604" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_94234faf-9aca-4e72-8712-4361532fa604_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_1ad6496d-f97d-4251-bb51-0bc8c93b118a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_94234faf-9aca-4e72-8712-4361532fa604" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_1ad6496d-f97d-4251-bb51-0bc8c93b118a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9d976317-8841-4f50-9606-c9434dd4ca17" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_1ad6496d-f97d-4251-bb51-0bc8c93b118a" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9d976317-8841-4f50-9606-c9434dd4ca17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_349b9335-c195-4504-bc59-567371574d44" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_1ad6496d-f97d-4251-bb51-0bc8c93b118a" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_349b9335-c195-4504-bc59-567371574d44" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/ShareBasedCompensationCompensationCostNotYetRecognizedDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#ShareBasedCompensationCompensationCostNotYetRecognizedDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/ShareBasedCompensationCompensationCostNotYetRecognizedDetails" xlink:type="extended" id="i5c5429ecc6234bb5a2bf9544b0b5a864_ShareBasedCompensationCompensationCostNotYetRecognizedDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_71bbe65f-033e-4903-abd0-520039968eaf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_9b22037d-ff21-4398-a4e2-52bff4826395" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_71bbe65f-033e-4903-abd0-520039968eaf" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_9b22037d-ff21-4398-a4e2-52bff4826395" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_362d7b12-b137-4cc2-b69a-bfdda0e34a41" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_71bbe65f-033e-4903-abd0-520039968eaf" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_362d7b12-b137-4cc2-b69a-bfdda0e34a41" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a799654f-1b16-4898-ba3f-74960fe3d21a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_71bbe65f-033e-4903-abd0-520039968eaf" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a799654f-1b16-4898-ba3f-74960fe3d21a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_1d0b88ad-d5d2-49cf-baf9-3b478d27416d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_a799654f-1b16-4898-ba3f-74960fe3d21a" xlink:to="loc_us-gaap_AwardTypeAxis_1d0b88ad-d5d2-49cf-baf9-3b478d27416d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1d0b88ad-d5d2-49cf-baf9-3b478d27416d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_1d0b88ad-d5d2-49cf-baf9-3b478d27416d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1d0b88ad-d5d2-49cf-baf9-3b478d27416d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7f9d9aaf-1538-4855-b9b8-e5f160cf6a78" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_1d0b88ad-d5d2-49cf-baf9-3b478d27416d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7f9d9aaf-1538-4855-b9b8-e5f160cf6a78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_fc7cf9ac-91ce-43a7-9c0b-d70ca1d88c64" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7f9d9aaf-1538-4855-b9b8-e5f160cf6a78" xlink:to="loc_us-gaap_EmployeeStockOptionMember_fc7cf9ac-91ce-43a7-9c0b-d70ca1d88c64" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_05aa3963-ace5-4601-9b5f-0fd145ab67b6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7f9d9aaf-1538-4855-b9b8-e5f160cf6a78" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_05aa3963-ace5-4601-9b5f-0fd145ab67b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockMember_efc44995-b449-47da-83f3-53d3a9f2ac37" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7f9d9aaf-1538-4855-b9b8-e5f160cf6a78" xlink:to="loc_us-gaap_RestrictedStockMember_efc44995-b449-47da-83f3-53d3a9f2ac37" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/ShareBasedCompensationFairValueofSharesVestedandWeightedAverageEstimatedFairValueofSharesGrantedDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#ShareBasedCompensationFairValueofSharesVestedandWeightedAverageEstimatedFairValueofSharesGrantedDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/ShareBasedCompensationFairValueofSharesVestedandWeightedAverageEstimatedFairValueofSharesGrantedDetails" xlink:type="extended" id="ia72ef5078af04f3eb4fc26ab5eac9187_ShareBasedCompensationFairValueofSharesVestedandWeightedAverageEstimatedFairValueofSharesGrantedDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_1cfc1bea-fb0b-4818-9587-e0ce76f888e2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_79dc4ed7-2d46-400a-b8bb-a7f98ab38be3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_1cfc1bea-fb0b-4818-9587-e0ce76f888e2" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_79dc4ed7-2d46-400a-b8bb-a7f98ab38be3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_890f1875-ecd3-4c29-a639-6543ab030c2f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_1cfc1bea-fb0b-4818-9587-e0ce76f888e2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_890f1875-ecd3-4c29-a639-6543ab030c2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b30453e7-96ff-46aa-9ee1-3c728af5c28b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_1cfc1bea-fb0b-4818-9587-e0ce76f888e2" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b30453e7-96ff-46aa-9ee1-3c728af5c28b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_c2217557-903c-4a5e-aa35-5018e37a7878" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b30453e7-96ff-46aa-9ee1-3c728af5c28b" xlink:to="loc_us-gaap_AwardTypeAxis_c2217557-903c-4a5e-aa35-5018e37a7878" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2217557-903c-4a5e-aa35-5018e37a7878_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_c2217557-903c-4a5e-aa35-5018e37a7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c2217557-903c-4a5e-aa35-5018e37a7878_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0ba012f6-a493-4bca-96ce-b8de3c34f0cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_c2217557-903c-4a5e-aa35-5018e37a7878" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0ba012f6-a493-4bca-96ce-b8de3c34f0cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_a9f843d0-c299-4a17-9be3-7e6f265a4bad" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_0ba012f6-a493-4bca-96ce-b8de3c34f0cf" xlink:to="loc_us-gaap_EmployeeStockOptionMember_a9f843d0-c299-4a17-9be3-7e6f265a4bad" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/ShareBasedCompensationValuationAssumptionsDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#ShareBasedCompensationValuationAssumptionsDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/ShareBasedCompensationValuationAssumptionsDetails" xlink:type="extended" id="ifed8086cd786428996e466382cd78a2b_ShareBasedCompensationValuationAssumptionsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2246c916-8f7a-40d2-9aec-2c2029fd0011" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2246c916-8f7a-40d2-9aec-2c2029fd0011" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_e0bd6021-a42b-4834-8d8e-82b8ead5becc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_e0bd6021-a42b-4834-8d8e-82b8ead5becc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_a95048c2-20bd-4b33-8d99-bdea663a7797" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_a95048c2-20bd-4b33-8d99-bdea663a7797" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_17b0cc26-3fbf-4d74-8d23-3da4aa5f7d78" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_17b0cc26-3fbf-4d74-8d23-3da4aa5f7d78" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_abbafd89-08f5-4304-98a4-1235f627f4f5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_abbafd89-08f5-4304-98a4-1235f627f4f5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_decbea84-6056-4526-a7c0-c725526c11b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_decbea84-6056-4526-a7c0-c725526c11b3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_dba4f02c-0d3b-4950-b991-5f73c53b8ef1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_dba4f02c-0d3b-4950-b991-5f73c53b8ef1" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_fc18106d-3433-4c95-8d11-2a7eef625caf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_2b203397-64a3-42fc-b63c-7b866bcce94b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_fc18106d-3433-4c95-8d11-2a7eef625caf" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0176f0fd-7836-40e1-bad8-2194f294af70" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_2246c916-8f7a-40d2-9aec-2c2029fd0011" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0176f0fd-7836-40e1-bad8-2194f294af70" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_404a235b-9017-4f48-83ed-79bcddfbd1a2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0176f0fd-7836-40e1-bad8-2194f294af70" xlink:to="loc_us-gaap_AwardTypeAxis_404a235b-9017-4f48-83ed-79bcddfbd1a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_404a235b-9017-4f48-83ed-79bcddfbd1a2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_404a235b-9017-4f48-83ed-79bcddfbd1a2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_404a235b-9017-4f48-83ed-79bcddfbd1a2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ac9abd70-58a6-4cfb-9281-c875da7ac185" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_404a235b-9017-4f48-83ed-79bcddfbd1a2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ac9abd70-58a6-4cfb-9281-c875da7ac185" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_945ca8aa-321f-48c9-8ad3-d9f195b5436b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ac9abd70-58a6-4cfb-9281-c875da7ac185" xlink:to="loc_us-gaap_EmployeeStockOptionMember_945ca8aa-321f-48c9-8ad3-d9f195b5436b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_abb9c82b-79e5-41f7-9d56-71168693f6d6" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_0176f0fd-7836-40e1-bad8-2194f294af70" xlink:to="loc_srt_RangeAxis_abb9c82b-79e5-41f7-9d56-71168693f6d6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_abb9c82b-79e5-41f7-9d56-71168693f6d6_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_abb9c82b-79e5-41f7-9d56-71168693f6d6" xlink:to="loc_srt_RangeMember_abb9c82b-79e5-41f7-9d56-71168693f6d6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b4d0f660-155a-4a32-baa9-978d61021d7b" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_abb9c82b-79e5-41f7-9d56-71168693f6d6" xlink:to="loc_srt_RangeMember_b4d0f660-155a-4a32-baa9-978d61021d7b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_312b9888-69ca-4bb9-9793-d72dedae7b8a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_b4d0f660-155a-4a32-baa9-978d61021d7b" xlink:to="loc_srt_MinimumMember_312b9888-69ca-4bb9-9793-d72dedae7b8a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_541ad866-3446-412a-a8b9-a3e08e7657c5" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_b4d0f660-155a-4a32-baa9-978d61021d7b" xlink:to="loc_srt_MaximumMember_541ad866-3446-412a-a8b9-a3e08e7657c5" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.caladrius.com/role/IncomeTaxesNarrativeDetails" xlink:type="simple" xlink:href="clbs-20211231.xsd#IncomeTaxesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.caladrius.com/role/IncomeTaxesNarrativeDetails" xlink:type="extended" id="id61b66e27f54441f8e8f381b3f57670f_IncomeTaxesNarrativeDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwardsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_3286fbe8-31f1-4967-bd94-4754e8057367" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate_3286fbe8-31f1-4967-bd94-4754e8057367" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_OperatingLossCarryforwardsBeforeWriteDown_c17be8d2-7b29-456b-8b16-c4facc20a02d" xlink:href="clbs-20211231.xsd#clbs_OperatingLossCarryforwardsBeforeWriteDown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_OperatingLossCarryforwardsBeforeWriteDown_c17be8d2-7b29-456b-8b16-c4facc20a02d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwards_eed24f5c-454d-41bd-b33a-359e4b4dfd30" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwards"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_us-gaap_OperatingLossCarryforwards_eed24f5c-454d-41bd-b33a-359e4b4dfd30" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_OperatingLossCarryforwardsSetToExpireWrittenDown_186eb707-1e4c-452e-ae3f-5136a54f10fe" xlink:href="clbs-20211231.xsd#clbs_OperatingLossCarryforwardsSetToExpireWrittenDown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_OperatingLossCarryforwardsSetToExpireWrittenDown_186eb707-1e4c-452e-ae3f-5136a54f10fe" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_OperatingLossCarryforwardsAnnualAvailableFiveYearsNetUnrealizedBuiltInGain_168a4478-844e-4993-a565-6613322c32c7" xlink:href="clbs-20211231.xsd#clbs_OperatingLossCarryforwardsAnnualAvailableFiveYearsNetUnrealizedBuiltInGain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_OperatingLossCarryforwardsAnnualAvailableFiveYearsNetUnrealizedBuiltInGain_168a4478-844e-4993-a565-6613322c32c7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgram_2ae5e589-a63e-41bc-aeb4-bc4b657ea5de" xlink:href="clbs-20211231.xsd#clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgram"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgram_2ae5e589-a63e-41bc-aeb4-bc4b657ea5de" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgramGross_ec1c928f-d66f-45d2-9c3b-d4ee8621c393" xlink:href="clbs-20211231.xsd#clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgramGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_ProceedsFromSaleOfNetOperatingLossesNJEDAProgramGross_ec1c928f-d66f-45d2-9c3b-d4ee8621c393" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_clbs_LossOnSaleOfNetOperatingLosses_bb4992b8-e7f5-4401-936b-369787eaf1c4" xlink:href="clbs-20211231.xsd#clbs_LossOnSaleOfNetOperatingLosses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_clbs_LossOnSaleOfNetOperatingLosses_bb4992b8-e7f5-4401-936b-369787eaf1c4" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_a3fd3435-87ab-4516-810c-6ed016db4845" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_8d97d55d-3dd1-4a24-b576-0947d70cfcb3" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_a3fd3435-87ab-4516-810c-6ed016db4845" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_d7955022-179b-4f51-8c4b-1849f7f1b41e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_a3fd3435-87ab-4516-810c-6ed016db4845" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_d7955022-179b-4f51-8c4b-1849f7f1b41e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_d7955022-179b-4f51-8c4b-1849f7f1b41e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_d7955022-179b-4f51-8c4b-1849f7f1b41e" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_d7955022-179b-4f51-8c4b-1849f7f1b41e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_7ebf5c78-d303-48d6-8483-66a8beabe0d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_d7955022-179b-4f51-8c4b-1849f7f1b41e" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_7ebf5c78-d303-48d6-8483-66a8beabe0d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_e45a25a3-a20b-4e38-a797-f324fb121569" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DomesticCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_7ebf5c78-d303-48d6-8483-66a8beabe0d2" xlink:to="loc_us-gaap_DomesticCountryMember_e45a25a3-a20b-4e38-a797-f324fb121569" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalJurisdictionMember_261cf2b0-5ed5-4023-94da-b598c24706b1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StateAndLocalJurisdictionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_7ebf5c78-d303-48d6-8483-66a8beabe0d2" xlink:to="loc_us-gaap_StateAndLocalJurisdictionMember_261cf2b0-5ed5-4023-94da-b598c24706b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityNameAxis_77619531-defa-4dc5-85a4-d5e5c78440fd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_a3fd3435-87ab-4516-810c-6ed016db4845" xlink:to="loc_us-gaap_IncomeTaxAuthorityNameAxis_77619531-defa-4dc5-85a4-d5e5c78440fd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityNameDomain_77619531-defa-4dc5-85a4-d5e5c78440fd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityNameAxis_77619531-defa-4dc5-85a4-d5e5c78440fd" xlink:to="loc_us-gaap_IncomeTaxAuthorityNameDomain_77619531-defa-4dc5-85a4-d5e5c78440fd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityNameDomain_0cccc6d6-16ee-4b0a-bbe8-0af2f32d61a8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityNameAxis_77619531-defa-4dc5-85a4-d5e5c78440fd" xlink:to="loc_us-gaap_IncomeTaxAuthorityNameDomain_0cccc6d6-16ee-4b0a-bbe8-0af2f32d61a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewJerseyDivisionOfTaxationMember_50bc98a2-f0a6-4795-a747-7049449707fb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewJerseyDivisionOfTaxationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityNameDomain_0cccc6d6-16ee-4b0a-bbe8-0af2f32d61a8" xlink:to="loc_us-gaap_NewJerseyDivisionOfTaxationMember_50bc98a2-f0a6-4795-a747-7049449707fb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CaliforniaFranchiseTaxBoardMember_22a34394-93cc-49b4-a104-bad8175c63cb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CaliforniaFranchiseTaxBoardMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityNameDomain_0cccc6d6-16ee-4b0a-bbe8-0af2f32d61a8" xlink:to="loc_us-gaap_CaliforniaFranchiseTaxBoardMember_22a34394-93cc-49b4-a104-bad8175c63cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewYorkStateDivisionOfTaxationAndFinanceMember_d54e9438-e06b-4817-8c4f-13586f7585a6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewYorkStateDivisionOfTaxationAndFinanceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityNameDomain_0cccc6d6-16ee-4b0a-bbe8-0af2f32d61a8" xlink:to="loc_us-gaap_NewYorkStateDivisionOfTaxationAndFinanceMember_d54e9438-e06b-4817-8c4f-13586f7585a6" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-roles-2021-01-31.xsd#eedm"/>
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract" xlink:to="loc_us-gaap_OtherAssetsNoncurrent" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrentAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
