Published online before print November 3, 2005, doi: 10.1161/01.RES.0000194330.66545.f5
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© 2005 American Heart Association, Inc.
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Restoration of Cardiac Progenitor Cells After Myocardial Infarction by Self-Proliferation and Selective Homing of Bone Marrow–Derived Stem Cells
From the Cardiovascular Division (F.M., O.P., M.J., A.O., S.N., R.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston; and The Pulmonary Center (R.S., A.F.), Boston University School of Medicine, Mass.
Correspondence to Dr Ronglih Liao, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 431, Boston, MA 02115. E-mail rliao{at}rics.bwh.harvard.edu
Tissue-specific progenitor cells contribute to local cellular regeneration and maintain organ function. Recently, we have determined that cardiac side-population (CSP) cells represent a distinct cardiac progenitor cell population, capable of in vitro differentiation into functional cardiomyocytes. The response of endogenous CSP to myocardial injury, however, and the cellular mechanisms that maintain this cardiac progenitor cell pool in vivo remain unknown. In this report we demonstrate that local progenitor cell proliferation maintains CSP under physiologic conditions, with little contribution from extracardiac stem cell sources. Following myocardial infarction in adult mice, however, CSP cells are acutely depleted, both within the infarct and noninfarct areas. CSP pools are subsequently reconstituted to baseline levels within 7 days after myocardial infarction, through both proliferation of resident CSP cells, as well as through homing of bone marrow–derived stem cells (BMC) to specific areas of myocardial injury and immunophenotypic conversion of BMC to adopt a CSP phenotype. We, therefore, conclude that following myocardial injury, cardiac progenitor cell populations are acutely depleted and are reconstituted to normal levels by both self-proliferation and selective homing of BMC. Understanding and enhancing such processes hold enormous potential for therapeutic myocardial regeneration.
Key Words: side population cells • cardiac progenitor cells • myocardial infarction • cardiomyogenesis
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