Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

被引：83
作者：
Zhao, Liyan [1 ]
Liu, Xiaolin [1 ]
Zhang, Yuelin [2 ]
Liang, Xiaoting [3 ]
Ding, Yue [3 ]
Xu, Yan [1 ]
Fang, Zhen [1 ]
Zhang, Fengxiang [1 ]
机构：
[1] Nanjing Med Univ, Affiliated Hosp 1, Div Cardiol, Sect Pacing & Electrophysiol, Nanjing, Jiangsu, Peoples R China
[2] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Div Cardiol, Hong Kong, Hong Kong, Peoples R China
[3] Tongji Univ, Shanghai East Hosp, Sch Med, Pudong Dist Clin Translat Med Res Ctr, Shanghai 200092, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2016年 / 344卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Mesenchymal stem cells; Hepatocyte growth factor; Myocardial infarction; Cytokines; ENDOTHELIAL-CELLS; PROLIFERATION; HEART; PATHOPHYSIOLOGY; CARDIOMYOCYTES; ENGRAFTMENT; ACTIVATION; THERAPY; HGF;
D O I：
10.1016/j.yexcr.2016.03.024
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-ARt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码：30 / 39
页数：10
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