Zhang Guang-Wei, Gu Tian-Xiang, Guan Xiao-Yu, Sun Xue-Jun, Qi Xun, Li Xue-Yuan, Wang Xiao-Bing, Lv Feng, Yu Lei, Jiang Da-Qing, Tang Rui
Department of Cardiac Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
The Cardiovascular Research Center of China Medical University, Shenyang, 110001, China.
Cell Prolif. 2015 Dec;48(6):661-70. doi: 10.1111/cpr.12219. Epub 2015 Oct 15.
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.
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 × 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 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.
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).
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.
探讨肝细胞生长因子（HGF）联合胰岛素样生长因子1（IGF-1）对移植骨髓间充质干细胞（BMSCs）的影响，用于治疗急性心肌缺血。
结扎左冠状动脉前降支后，将兔分为对照组、因子组（HGF+IGF-1）、BMSC组和因子+BMSC组。将同种异体BMSCs（1×10⁷）和/或含2μg HGF+2μg IGF-1的控释微球心肌内注射到梗死区域。在不同时间点评估植入BMSCs的凋亡与分化、组织学和形态学结果以及心脏重塑和功能。体外实验中，将BMSCs暴露于HGF、IGF-1及两者（50ng/ml），随后分析缺氧诱导的增殖、迁移、心肌分化和凋亡情况。
术后4周，因子+BMSC组上述指标较其他组显著改善（P<0.01），尽管因子组和BMSC组也比对照组有更好的结果（P<0.05）。体外实验中，HGF促进BMSC迁移并分化为心肌细胞，但抑制增殖（P<0.05），而IGF-1增加增殖和迁移，并抑制缺氧诱导的凋亡（P<0.05），但不诱导心肌分化。HGF与IGF-1联合显著促进BMSCs的迁移、分化能力且无凋亡（P<0.05）。
HGF与IGF-1联合可互补激活BMSCs，两种因子的控释促进了移植BMSCs修复梗死心肌的保护潜能。这提示了一种克服急性缺血性心肌损伤的细胞治疗新策略。
