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

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• 作者：Liyan Zhao^a ; ¹ ; Xiaolin Liu^a ; ¹ ; Yuelin Zhang^b ; Xiaoting Liang^c ; Yue Ding^c ; Yan Xu^a ; Zhen Fang^a ; Fengxiang Zhang^a ; ^{njzfx6@njmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：bFGF ; basic fibroblast growth factor ; CdM ; conditioned medium ; EGF ; epidermal growth factor ; ELISA ; enzyme-linked immunosorbent assay ; GFP ; green fluorescent protein ; HGF ; hepatocyte growth factor ; LVESP ; left ventricle end systolic pressure ; LVEDP ; left ventricular end diastolic pressure ; MSCs ; mesenchymal stem cells ; MI ; myocardial infarction ; NCMs ; neonatal cardiomyocytes ; PCR ; polymerase chain reaction ; TUNEL ; terminal deoxynucleotidyl transferase DUTP nick end labeling ; UC ; umbilical cord
• 刊名：Experimental Cell Research
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：344
• 期：1
• 页码：30-39
• 全文大小：10619 K

文摘

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-Akt 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.