Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats.
The aim of this study was to investigate whether the modification of bone marrow-derived mesenchymal stem cells (BMSCs) with the fused FGF4 (fibroblast growth factor 4)-bFGF (basic fibroblast growth factor) gene could improve the expression and secretion of BFGF, and increase the efficacies in repairing infarcted myocardium. We used In-Fusion technique to construct recombinant lentiviral vectors containing the individual gene of bFGF, enhanced green fluorescent protein (EGFP), or genes of FGF4-bFGF and EGFP, and then transfected these lentiviruses into rat BMSCs. We conducted an in vitro experiment to compare the secretion of bFGF in BMSCs infected by these lentiviruses and also examined their therapeutic effects in the treatment of myocardial infraction in a rodent study. Sixty rats were tested in the following five conditions: Group-SHAM received only sham operation as controls; Group-AMI received only injection of placebo PBS buffer; Group-BMSC, Group-bFGF and Group-FGF4-bFGF received implantation of BMSCs with empty lentivirus, bFGF lentivirus, and FGF4-bFGF lentivirus, respectively. Our results found out that the transplanted FGF4-bFGF BMSCs had the highest survival rate, and also the highest myocardial expression of bFGF and microvascular density as evidenced by Western blotting and immunohistochemistry, respectively. As compared to other groups, the Group-FGF4-BFGF rats had the lowest myocardial fibrotic fraction, and the highest left ventricular ejection fraction. These results suggest that the modification of BMSCs with the FGF4-bFGF fused gene can not only increase the expression of bFGF but also improve its secretion. The FGF4-bFGF BMSCs thus can enhance the survival of the transplanted cells, diminish myocardial fibrosis, promote myocardial angiogenesis, and improve cardiac functions.
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.
Xiang-Qi
XQ
Chen
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China. Electronic address: xhzlyx@126.com.
Liang-Long
LL
Chen
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.
Lin
L
Fan
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.
Jun
J
Fang
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.
Zhao-Yang
ZY
Chen
Fujian Institute of Coronary Artery Disease and Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China.
Wei-Wei
WW
Li
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D051519:Fibroblast Growth Factor 4 / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000627:therapeutic use; D014162:Transfection
C496447:Fgf4 protein, rat; D051519:Fibroblast Growth Factor 4; D011993:Recombinant Fusion Proteins; D016222:Fibroblast Growth Factor 2
Basic fibroblast growth factor; Bone marrow-derived mesenchymal stem cells; Myocardial infarction; Transplantation; Treatment