title: Enhanced therapeutic effects of mesenchymal stem cells on myocardial infarction by ischemic postconditioning through paracrine mechanisms in rats.
abstract: Ischemic postconditioning (IPC) is cardioprotective against ischemia-reperfusion injury which impairs the myocardial micro-environment and reduces the survival of transplanted cells. We tested the hypothesis that IPC may improve the survival of transplanted cells and enhance their therapeutic effects. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) from Sprague-Dawley rats were infected with lentivirus carrying green fluorescent protein (GFP) gene. The left main coronary arteries of rats were occluded for a 30-min ischemia, followed by a 72 h or 28 d reperfusion. IPC was induced by 3 cycles of 10s reperfusion and 10s ischemia before sustained reperfusion. GFP-BMSCs were intramyocardially injected at 2h reperfusion. At 70 h after transplantation, IPC treatment increased the level of interleukin-10, B-cell leukemia-lymphoma-2 (BCL-2), and vascular endothelial and basic fibroblast growth factor (VEGF and bFGF), and decreased the level of tumor necrosis factor-α, interleukin-1β and BCL-2-associated X protein by ELISA or PCR or western blotting. The BMSCs therapy with IPC produced more surviving GFP-positive cells than the BMSCs therapy alone by fluorescent staining [at 70 h, (90 ± 14)/mm(2) vs. (61 ± 12)/mm(2), and at 28 days, (55 ± 14)/mm(2) vs. (26 ± 8)/mm(2), P<0.01, respectively]. At 28 days, it, when compared with the Control, IPC treatment, and BMSCs therapy, demonstrated higher left ventricular ejection fraction by echocardiography (62%± 8%, 69%± 6%, and 75%± 4% vs. 82%± 4%, P<0.05, respectively), higher expression of VEGF and bFGF by western blotting and PCR, less myocardial fibrosis by Masson's trichrome staining, and higher capillary density by immunohistochemistry. These results suggest that ischemic postconditioning promotes the survival of transplanted cells and enhances their repair of infarcted myocardium through paracrine mechanisms.
authors.affiliation: Department of Cardiology, the Affiliated Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, 350001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Lianglong
authors.initials: L
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.forename: Liming
authors.initials: L
authors.lastname: Wu
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Yunling
authors.initials: Y
authors.lastname: Lin
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D004452:Echocardiography; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods*; D016086:Lentivirus; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D049452:Green Fluorescent Proteins