Wang Xiaohong, Hu Qingsong, Nakamura Yasuhiro, Lee Joseph, Zhang Ge, From Arthur H L, Zhang Jianyi
Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, 55455, USA.
Stem Cells. 2006 Jul;24(7):1779-88. doi: 10.1634/stemcells.2005-0386. Epub 2006 Apr 13.
Cardiac stem cell-like populations exist in adult hearts, and their roles in cardiac repair remain to be defined. Sca-1 is an important surface marker for cardiac and other somatic stem cells. We hypothesized that heart-derived Sca-1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro could be induced to express both endothelial cell and cardiomyocyte markers. Immunofluorescence staining and fluorescence-activated cell sorting analysis indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in the mouse heart 7 days after myocardial infarction (MI). Western blotting confirmed elevated Sca-1 protein expression in myocardium 7 days after MI. Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart attenuated the functional decline and adverse structural remodeling initiated by MI as evidenced by an increased left ventricular (LV) ejection fraction, a decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a significant increase of myocardial neovascularization, and modest cardiomyocyte regeneration. Attenuation of LV remodeling was accompanied by remarkably improved myocardial bioenergetic characteristics. The beneficial effects of cell transplantation appear to primarily depend on paracrine effects of the transplanted cells on new vessel formation and native cardiomyocyte function. Sca-1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the treatment of ischemic heart disease.
成年心脏中存在类心脏干细胞群体，它们在心脏修复中的作用尚待明确。Sca-1是心脏及其他体干细胞的重要表面标志物。我们推测，心脏来源的Sca-1(+)/CD31(-)细胞可能在心肌梗死诱导的心脏修复/重塑中发挥作用。体外培养的小鼠心脏来源的Sca-1(+)/CD31(-)细胞可被诱导表达内皮细胞和心肌细胞标志物。免疫荧光染色和荧光激活细胞分选分析表明，心肌梗死后7天，小鼠心脏中内源性Sca-1(+)/CD31(-)细胞显著增加。蛋白质印迹法证实心肌梗死后7天心肌中Sca-1蛋白表达升高。将Sca-1(+)/CD31(-)细胞移植到急性梗死的小鼠心脏中，可减轻心肌梗死引发的功能衰退和不良结构重塑，表现为左心室射血分数增加、左心室舒张末期内径减小、左心室收缩末期内径减小、心肌新生血管形成显著增加以及适度的心肌细胞再生。左心室重塑的减轻伴随着心肌生物能量特征的显著改善。细胞移植的有益作用似乎主要取决于移植细胞对新血管形成和天然心肌细胞功能的旁分泌作用。Sca-1(+)/CD31(-)细胞在缺血性心脏病的治疗方面可能具有治疗潜力。
