Open AccessMigration of bone marrow‐derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction
Author(s) -
Brunner Stefan,
Huber Bruno C.,
Weinberger Tobias,
Vallaster Marcus,
Wollenweber Tim,
Gerbitz Armin,
Hacker Marcus,
Franz WolfgangMichael
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01286.x
Subject(s) - bone marrow , erythropoietin , perfusion , medicine , homing (biology) , neovascularization , myocardial infarction , angiogenesis , pathology , biology , ecology
Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor‐dependent mechanisms, mobilization and homing of bone marrow‐derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO‐treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c‐kit, CXCR‐4 and Sca‐1) of EGFP + cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single‐photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO‐treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO‐treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR‐4 + (4.3‐fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively.