Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor.
Mesenchymal stem cells could differentiate into cardiomyocytes in vitro and have been shown to reconstitute the impaired myocardium in vivo. Hepatocyte growth factor, a recognized angiogenic factor and endothelial cell chemoattractant, has been applied in the treatment of myocardial ischemia. In this study, we used a ligation model of proximal left anterior descending coronary artery of rats to evaluate the effect of mesenchymal stem cells overexpressing hepatocyte growth factor in the treatment of myocardial ischemia. Bone marrow-derived mesenchymal stem cells were isolated, expanded, characterized, and infected with adenovirus carrying human hepatocyte growth factor cDNA (Ad-HGF). Mesenchymal stem cells infected by Ad-HGF released soluble HGF protein at a high level, which was maintained at least for 2 weeks. Implantation of mesenchymal stem cells overexpressing hepatocyte growth factor into left anterior descending risk areas improved the functions of impaired myocardium, including diminishing the area of ischemia, increasing the number of capillaries, and reducing collagen content. By using the sry gene as a marker, we also demonstrated that the engrafted cells or their progeny incorporated into ischemic cardiac muscle. These results showed that treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor could be a novel strategy that can both restore local blood flow and regenerate lost cardiomyocytes.
Duan
Hai-Feng
HF
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, 100850, Beijing, People's Republic of China.
Wu
Chu-Tse
CT
Wu
Dan-Li
DL
Lu
Ying
Y
Liu
Hong-Jun
HJ
Ha
Xiao-Qin
XQ
Zhang
Qun-Wei
QW
Wang
Hua
H
Jia
Xiang-Xu
XX
Wang
Li-Sheng
LS
D000256:Adenoviridae; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
D017228:Hepatocyte Growth Factor