Combined transplantation of endothelial progenitor cells and mesenchymal stem cells into a rat model of isoproterenol-induced myocardial injury.
BACKGROUND
Endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have different biological properties, but their potential for synergy in the treatment of injured myocardium has not been studied extensively.


OBJECTIVE
To determine if outcome could be improved by simultaneously transplanting MSCs and EPCs into a rat model of isoproterenol (ISO)-induced injured myocardium.


METHODS
Four weeks after ISO injection, 50 rats were separated randomly into five groups (n=10 per group) and allocated to receive a saline injection (control group), 200 microL medium alone, 200 microL medium plus 2x10(6) EPCs, 200 microL medium plus 2x10(6) MSCs, or 200 microL medium plus a combination of 1x10(6) EPCs and 1x10(6) MSCs. Echocardiography and invasive catheterization were performed to evaluate dynamic changes in cardiac performance, 12 weeks after treatment administration.


RESULTS
Transplanted cells were detected in myocardial tissue by fluorescence in situ hybridization, indicating either differentiation or integration into cardiac tissue cells. The group of rats that received both EPCs and MSCs had an increased level of angiogenic growth factors expression, less collagen deposition, fewer apoptotic cells and an improved regional myocardial blood flow compared with the other groups; these effects resulted in greater enhancement of cardiac function in that group.


CONCLUSIONS
Transplantation of EPCs combined with MSCs may represent a novel and efficient therapeutic strategy for enhancing regional myocardial blood flow and improving cardiac function in injured myocardium.
Zhang
Xin
X
Division of Cardiology, Shanghai Sixth Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Wei
Meng
M
Zhu
Wei
W
Han
Beibei
B
D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000009:adverse effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007545:Isoproterenol / Q000009:adverse effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008863:Microspheres; D009203:Myocardial Infarction / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D012039:Regional Blood Flow; D051876:Sex-Determining Region Y Protein / Q000378:metabolism; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042702:Angiopoietin-2; D002316:Cardiotonic Agents; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D007545:Isoproterenol