The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling.
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.
Wang
Xiaohong
X
Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, 55455, USA. wangx270@umn.edu
Hu
Qingsong
Q
Nakamura
Yasuhiro
Y
Lee
Joseph
J
Zhang
Ge
G
From
Arthur H L
AH
Zhang
Jianyi
J
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism; D004734:Energy Metabolism; D005434:Flow Cytometry; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D024510:Muscle Development / Q000502:physiology; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000534:rehabilitation*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1