Mouquet Frédéric, Pfister Otmar, Jain Mohit, Oikonomopoulos Angelos, Ngoy Soeun, Summer Ross, Fine Alan, Liao Ronglih
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circ Res. 2005 Nov 25;97(11):1090-2. doi: 10.1161/01.RES.0000194330.66545.f5. Epub 2005 Nov 3.
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.
组织特异性祖细胞有助于局部细胞再生并维持器官功能。最近，我们确定心脏侧群（CSP）细胞代表一种独特的心脏祖细胞群体，能够在体外分化为功能性心肌细胞。然而，内源性CSP对心肌损伤的反应以及在体内维持这种心脏祖细胞库的细胞机制仍不清楚。在本报告中，我们证明在生理条件下，局部祖细胞增殖维持CSP，心脏外干细胞来源的贡献很小。然而，在成年小鼠心肌梗死后，梗死区和非梗死区的CSP细胞均急剧减少。心肌梗死后7天内，CSP库随后通过驻留CSP细胞的增殖以及骨髓来源干细胞（BMC）归巢至心肌损伤的特定区域并将BMC免疫表型转化为CSP表型而恢复至基线水平。因此，我们得出结论，心肌损伤后，心脏祖细胞群体急剧减少，并通过BMC的自我增殖和选择性归巢而恢复至正常水平。了解并增强这些过程对于治疗性心肌再生具有巨大潜力。
