Exosomes from mesenchymal stem cells overexpressing MIF enhance myocardial repair

被引：104
作者：
Liu, Xiaolin [1 ]
Li, Xin [2 ,3 ]
Zhu, Wenwu [1 ]
Zhang, Yuelin [2 ,3 ]
Hong, Yimei [2 ,3 ]
Liang, Xiaoting [4 ]
Fan, Baohan [1 ]
Zhao, Hongyan [1 ]
He, Haiwei [2 ,3 ]
Zhang, Fengxiang [1 ]
机构：
[1] Nanjing Med Univ, Affiliated Hosp 1, Div Cardiol, Sect Pacing & Electrophysiol, Guangzhou Rd 300, Nanjing 210029, Peoples R China
[2] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Emergency Med, Guangzhou, Peoples R China
[3] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Emergency & Crit Care Med, Guangzhou, Peoples R China
[4] Tongji Univ, Sch Med, Shanghai East Hosp, Clin Translat Med Res Ctr, Shanghai, Peoples R China
来源：
JOURNAL OF CELLULAR PHYSIOLOGY | 2020年 / 235卷 / 11期
关键词：
apoptosis; cardiomyocytes; exosome; macrophage migration inhibitory factor; mesenchymal stem cells; myocardial infarction; MIGRATION INHIBITORY FACTOR; MITOCHONDRIAL FISSION; SENESCENCE; AMPK; CARDIOPROTECTION; AUTOPHAGY; HEART;
D O I：
10.1002/jcp.29456
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Accumulating evidence has shown that mesenchymal stem cell (MSC)-derived exosomes (exo) mediate cardiac repair following myocardial infarction (MI). Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, plays a critical role in regulating cell homeostasis. This study aimed to investigate the cardioprotective effects of exo secreted from bone marrow-MSCs (BM-MSCs) overexpressing MIF in a rat model of MI. MIF plasmid was transducted in BM-MSCs. Exo were isolated from the supernatants of BM-MSCs and MIF-BM-MSCs, respectively. The morphology of mitochondria in neonatal mice cardiomyocytes (NRCMs) was determined by MitoTracker staining. The apoptosis of NRCMs was examined by deoxynucleotidyl transferase-mediated dUTP nick end-labeling. BM-MSC-exo and MIF-BM-MSC-exo were intramuscularly injected into the peri-infarct region in a rat model of MI. The heart function of rats was assessed by echocardiography. The expression of MIF was greatly enhanced in MIF-BM-MSCs compared with BM-MSCs. Both BM-MSC-exo and MIF-BM-MSC-exo expressed CD63 and CD81. NRCMs treated with MIF-BM-MSC-exo exhibited less mitochondrial fragmentation and cell apoptosis under hypoxia/serum deprivation (H/SD) challenge than those treated with BM-MSC-exo via activating adenosine 5 '-monophosphate-activated protein kinase signaling. Moreover, these effects were partially abrogated by Compound C. Injection of BM-MSC-exo or MIF-BM-MSC-exo greatly restored heart function in a rat model of MI. Compared with BM-MSC-exo, injection of MIF-BM-MSC-exo was associated with enhanced heart function, reduced heart remodeling, less cardiomyocyte mitochondrial fragmentation, reactive oxygen species generation, and apoptosis. Our study reveals a new mechanism of MIF-BM-MSC-exo-based therapy for MI and provides a novel strategy for cardiovascular disease treatment.
引用
收藏
页码：8010 / 8022
页数：13
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