PMID- 26466964 OWN - NLM STAT- MEDLINE DCOM- 20160426 LR - 20200315 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 48 IP - 6 DP - 2015 Dec TI - HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction. PG - 661-70 LID - 10.1111/cpr.12219 [doi] AB - OBJECTIVES: To explore effects of hepatocyte growth factor (HGF) combined with insulin-like growth factor 1 (IGF-1) on transplanted bone marrow mesenchymal stem cells (BMSCs), for treatment of acute myocardial ischaemia. MATERIALS AND METHODS: After ligation of the left anterior descending artery, rabbits were divided into a Control group, a Factors group (HGF+IGF-1), a BMSC group and a Factors+BMSCs group. Allogenous BMSCs (1 x 10(7)) and/or control-released microspheres of 2 mug HGF+2 mug IGF-1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSCs, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro, BMSCs were exposed to HGF, IGF-1 and both (50 ng/ml) and subsequently proliferation, migration, myocardial differentiation and apoptosis induced by hypoxia, were analysed. RESULTS: Four weeks post-operatively, the above indices were significantly improved in Factors+BMSCs group compared to the others (P < 0.01), although Factors and BMSCs group also showed better results than Control group (P < 0.05). In vitro, HGF promoted BMSC migration and differentiation into cardiomyocytes, but inhibited proliferation (P < 0.05), while IGF-1 increased proliferation and migration, and inhibited apoptosis induced by hypoxia (P < 0.05), but did not induce myocardial differentiation. Combination of HGF and IGF-1 significantly promoted BMSCs capacity for migration, differentiation and lack of apoptosis (P < 0.05). CONCLUSIONS: Combination of HGF and IGF-1 activated BMSCs complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSCs to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury. CI - (c) 2015 John Wiley & Sons Ltd. FAU - Zhang, Guang-Wei AU - Zhang GW AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Gu, Tian-Xiang AU - Gu TX AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. AD - The Cardiovascular Research Center of China Medical University, Shenyang, 110001, China. FAU - Guan, Xiao-Yu AU - Guan XY AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Sun, Xue-Jun AU - Sun XJ AD - Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Department of Anesthesiology of the First Affiliated Hospital of Dalian Medical University, Dalian, 116000, China. FAU - Qi, Xun AU - Qi X AD - Department of Radiology, The First Hospital of China Medical University, Shenyang, 110001, China. AD - Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Li, Xue-Yuan AU - Li XY AD - Department of Cardiology, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Wang, Xiao-Bing AU - Wang XB AD - Department of Echocardiography, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Lv, Feng AU - Lv F AD - Institute of Biomedical Engineering, Peking Union Medical College, Beijing, 100010, China. FAU - Yu, Lei AU - Yu L AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Jiang, Da-Qing AU - Jiang DQ AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. FAU - Tang, Rui AU - Tang R AD - Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151015 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 67763-96-6 (Insulin-Like Growth Factor I) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Bone Marrow Cells/cytology MH - Bone Marrow Transplantation MH - Cell Differentiation/drug effects MH - Cell Hypoxia/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Coronary Vessels/surgery MH - Disease Models, Animal MH - Drug Therapy, Combination MH - Hepatocyte Growth Factor/*therapeutic use MH - Insulin-Like Growth Factor I/*therapeutic use MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Myocardial Infarction/*drug therapy MH - Myocytes, Cardiac/*cytology MH - Neovascularization, Physiologic/drug effects MH - Rabbits PMC - PMC6496765 COIS- None declared. EDAT- 2015/10/16 06:00 MHDA- 2016/04/27 06:00 PMCR- 2015/10/15 CRDT- 2015/10/16 06:00 PHST- 2015/05/27 00:00 [received] PHST- 2015/07/29 00:00 [accepted] PHST- 2015/10/16 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2016/04/27 06:00 [medline] PHST- 2015/10/15 00:00 [pmc-release] AID - CPR12219 [pii] AID - 10.1111/cpr.12219 [doi] PST - ppublish SO - Cell Prolif. 2015 Dec;48(6):661-70. doi: 10.1111/cpr.12219. Epub 2015 Oct 15.