Haemin pre-treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

被引：40

作者：

Deng, Rui ^{[1
]}

Liu, Yaming ^{[2
]}

He, Haiwei ^{[3
]}

Zhang, Hao ^{[2
]}

Zhao, Chenling ^{[4
]}

Cui, Zhen ^{[5
]}

Hong, Yimei ^{[3
]}

Li, Xin ^{[3
]}

Lin, Fang ^{[6
]}

Yuan, Dongsheng ^{[6
]}

Liang, Xiaoting ^{[6
]}

Zhang, Yuelin ^{[2
,3
]}

机构：

[1] Bengbu Med Coll, Dept Gen Surg, Affiliated Hosp 2, Bengbu, Peoples R China

[2] Bengbu Med Coll, Sch Pharm, Bengbu, Anhui, Peoples R China

[3] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Emergency Med, Guangzhou, Guangdong, Peoples R China

[4] Bengbu Med Coll, Dept Resp Med, Affiliated Hosp 1, Bengbu, Peoples R China

[5] Bengbu Med Coll, Dept Radiat Oncol, Affiliated Hosp 1, Bengbu, Peoples R China

[6] Tongji Univ, Shanghai East Hosp, Clin Translat Med Res Ctr, Sch Med, Shanghai, Peoples R China

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2020年 / 24卷 / 01期

关键词：

cell survival; haem oxygenase-1; haemin; mesenchymal stem cells; mitochondrial fission; myocardial infarction; MYOCARDIAL-INFARCTION; OXYGENASE-1; DYNAMICS; MSCS;

D O I：

10.1111/jcmm.14747

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The cardiac protection of mesenchymal stem cell (MSC) transplantation for myocardial infarction (MI) is largely hampered by low cell survival. Haem oxygenase 1 (HO-1) plays a critical role in regulation of cell survival under many stress conditions. This study aimed to investigate whether pre-treatment with haemin, a potent HO-1 inducer, would promote the survival of MSCs under serum deprivation and hypoxia (SD/H) and enhance the cardioprotective effects of MSCs in MI. Bone marrow (BM)-MSCs were pretreated with or without haemin and then exposed to SD/H. The mitochondrial morphology of MSCs was determined by MitoTracker staining. BM-MSCs and haemin-pretreated BM-MSCs were transplanted into the peri-infarct region in MI mice. SD/H induced mitochondrial fragmentation, as shown by increased mitochondrial fission and apoptosis of BM-MSCs. Pre-treatment with haemin greatly inhibited SD/H-induced mitochondrial fragmentation and apoptosis of BM-MSCs. These effects were partially abrogated by knocking down HO-1. At 4 weeks after transplantation, compared with BM-MSCs, haemin-pretreated BM-MSCs had greatly improved the heart function of mice with MI. These cardioprotective effects were associated with increased cell survival, decreased cardiomyocytes apoptosis and enhanced angiogenesis. Collectively, our study identifies haemin as a regulator of MSC survival and suggests a novel strategy for improving MSC-based therapy for MI.

引用

页码：431 / 440

页数：10

共 34 条

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