Open AccessHGF and IGF ‐1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction
Author(s) -
Zhang GuangWei,
Gu TianXiang,
Guan XiaoYu,
Sun XueJun,
Qi Xun,
Li XueYuan,
Wang XiaoBing,
Lv Feng,
Yu Lei,
Jiang DaQing,
Tang Rui
Publication year - 2015
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12219
Subject(s) - hepatocyte growth factor , mesenchymal stem cell , apoptosis , transplantation , andrology , ligation , in vitro , chemistry , growth factor , immunology , medicine , pathology , receptor , biochemistry
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 ( BMSC s), 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+ BMSC s group. Allogenous BMSC s (1 × 10 7 ) and/or control‐released microspheres of 2 μg HGF +2 μg IGF ‐1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSC s, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro , BMSC s 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+ BMSC s group compared to the others ( P < 0.01), although Factors and BMSC s 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 BMSC s capacity for migration, differentiation and lack of apoptosis ( P < 0.05). Conclusions Combination of HGF and IGF ‐1 activated BMSC s complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSC s to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury.