Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice.
Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1-positive (Sca-1-positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway.
Matsuura
Katsuhisa
K
Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan. mkatu2002@yahoo.co.jp
Honda
Atsushi
A
Nagai
Toshio
T
Fukushima
Noritoshi
N
Iwanaga
Koji
K
Tokunaga
Masakuni
M
Shimizu
Tatsuya
T
Okano
Teruo
T
Kasanuki
Hiroshi
H
Hagiwara
Nobuhisa
N
Komuro
Issei
I
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D039041:Integrin alpha4beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology*; D051381:Rats; D033581:Stem Cell Transplantation; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000502:physiology
D039041:Integrin alpha4beta1; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A