Transplantation of healthy but not diabetic outgrowth endothelial cells could rescue ischemic myocardium in diabetic rabbits.
OBJECTIVE
There are two types of endothelial progenitor cell (EPC) in circulation, early EPC and outgrowth endothelial cell (OEC). Diabetes impairs the function of EPC, but it is not clear whether transplantation of OECs can rescue ischemic myocardium in diabetes. In this study, we compared the function of diabetic and healthy OECs in vitro. Then we administered diabetic and healthy OECs intramyocardially and compared their contribution to vasculogenesis in diabetic rabbits.


METHODS
Outgrowth endothelial cells from diabetic and healthy rabbits were isolated and subjected to in vitro proliferation, tube-forming, angiogenic cytokine assays. Exogenous diabetic and healthy OECs were analyzed for therapeutic efficacy in an acute ischemia model of diabetic rabbits. LV function was assessed using echocardiography. The capillary density and fibrosis area were evaluated. MRNA expression of VEGF and bFGF was analyzed using relative realtime quantitive PCR.


RESULTS
Proliferation, tube-forming, secretion of VEGF and bFGF of diabetic OECs were significantly reduced compared with healthy OECs. In diabetic rabbits, healthy OECs transplantation could increase capillary density and improve cardiac function, decrease fibrosis area compared with diabetic OEC and the control group. Real time PCR indicated that mRNA expression of VEGF and bFGF were augmented more in the healthy OEC group than those in the control and diabetic OEC groups.


CONCLUSIONS
These findings suggest that diabetes impairs the function of OECs. Transplantation of healthy OECs may rescue the ischemic myocardium by neovasculogenesis and paracrine effect in diabetic rabbits. However, autologous transplantation of diabetic OEC could not enhance cardiac function.
Tan
Qiang
Q
Department of Cardiology, The First Hospital of Qinhuangdao, Hebei Medical University, Qinhuangdao, Hebei, China.
Qiu
Lugui
L
Li
Guangping
G
Li
Changhong
C
Zheng
Chenghuan
C
Meng
Hengxing
H
Yang
Wansong
W
D000818:Animals; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D008297:Male; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011817:Rabbits; D033581:Stem Cell Transplantation; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis; D016277:Ventricular Function, Left / Q000502:physiology
D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2