Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium.
Neovascularization induced by vascular endothelial growth factor (VEGF) represents an appealing approach for treating ischemic heart disease. However, VEGF therapy has been associated with transient therapeutic effects and potential risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone marrow are a promising source for tissue regeneration and repair. In order to achieve a safe and persistent angiogenic effect, we have explored the potential of autologous MSCs transplantation to enhance angiogenesis and cardiac function of ischemic hearts. One week after myocardial infarction induced by occlusion of left anterior descending artery, autologous MSCs expanded in vitro was administrated intramyocardially into the infarct area of the same donor rats. By 2 months, MSCs implantation significantly elevated VEGF expression levels, accompanied by increased vascular density and regional blood flow in the infarct zone. The neovascularization resulted in a decreased apoptosis of hypertrophied myocytes and markedly improved the left ventricular contractility (ejection fraction: 79.9+/-7.6% vs. 37.2+/-6.9% in control animals). Therefore, mechanisms underlying MSCs improvement of cardiac functions may involve neovascularization induced by differentiation of MSCs to endothelial cells and para-secretion of growth factors, in addition to the apoptosis reduction and previously reported cardiomyocytes regeneration. Two months after cell transplantation, there are significant improvement of left ventricular function. Hence, autologous MSCs transplantation may represent a promising therapeutic strategy free of ethical concerns and immune rejection, for neovascularization in ischemic heart diseases.
Tang
Yao Liang
YL
Department of Pediatrics, College of Medicine and All Children's Hospital Research Institute, University of South Florida, 140 7th Avenue S, CRI 2007, St. Petersburg, FL 33701, USA.
Zhao
Qiang
Q
Zhang
Y Clare
YC
Cheng
Leilei
L
Liu
Mingya
M
Shi
Jianhui
J
Yang
Yin Zeng
YZ
Pan
Chuizhen
C
Ge
Junbo
J
Phillips
M Ian
MI
D043925:Angiogenesis Inducing Agents; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D006391:Hemangioma / Q000150:complications; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D033581:Stem Cell Transplantation / Q000662:veterinary; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D016276:Ventricular Function
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A