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
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
收藏
页码:431 / 440
页数:10
相关论文
共 34 条
[1]
Mitochondrial Dynamics - Mitochondrial Fission and Fusion in Human Diseases [J].
Archer, Stephen L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (23) :2236-2251
[2]
Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium [J].
Blocki, Anna ;
Beyer, Sebastian ;
Dewavrin, Jean-Yves ;
Goralczyk, Anna ;
Wang, Yingting ;
Peh, Priscilla ;
Ng, Michael ;
Moonshi, Shehzandi S. ;
Vuddagiri, Susmitha ;
Raghunath, Michael ;
Martinez, Eliana C. ;
Bhakoo, Kishore .
BIOMATERIALS, 2015, 53 :12-24
[3]
Myocardial infarction: stem cell transplantation for cardiac regeneration [J].
Carvalho, Edmund ;
Verma, Paul ;
Hourigan, Kerry ;
Banerjee, Rinti .
REGENERATIVE MEDICINE, 2015, 10 (08) :1025-1043
[4]
Chan DC., 2006, CELL, V125, P1241
[5]
Sphingosine 1-phosphate promotes mesenchymal stem cell-mediated cardioprotection against myocardial infarction via ERK1/2-MMP-9 and Akt signaling axis [J].
Chen, Ruirui ;
Cai, Xiqiang ;
Liu, Jing ;
Bai, Baobao ;
Li, Xue .
LIFE SCIENCES, 2018, 215 :31-42
[6]
Mesenchymal stem cells overexpressing heme oxygenase-1 ameliorate lipopolysaccharide-induced acute lung injury in rats [J].
Chen, Xuxin ;
Wu, Shanshan ;
Tang, Lu ;
Ma, Lei ;
Wang, Fan ;
Feng, Huasong ;
Meng, Jiguang ;
Han, Zhihai .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (05) :7301-7319
[7]
Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells [J].
Chen, Xuxin ;
Zhang, Yinliang ;
Wang, Wenjing ;
Liu, Zhenqian ;
Meng, Jiguang ;
Han, Zhihai .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 49 (01) :101-122
[8]
Blocking Nox2 improves mesenchymal stem cells therapy in myocardial infarction via antagonizing oxidant and promoting survival [J].
Feng, Dan ;
Zhang, Lai ;
Ding, Fengzhi ;
Yang, Fan ;
Ma, Wenya ;
Han, Zhenbo ;
Hua, Bingjie ;
Wang, Xiuxiu ;
Yu, Ying ;
Huang, Qi ;
Lei, Lei ;
Pan, Zhenwei ;
Cai, Benzhi .
JOURNAL OF CELLULAR PHYSIOLOGY, 2018, 233 (10) :7004-7015
[9]
Haemin attenuates intermittent hypoxia-induced cardiac injury via inhibiting mitochondrial fission [J].
Han, Qian ;
Li, Guihua ;
Ip, Mary SiuMan ;
Zhang, Yuelin ;
Zhen, Zhe ;
Mak, Judith ChoiWo ;
Zhang, Nuofu .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2018, 22 (05) :2717-2726
[10]
Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model [J].
Han, Yong-seok ;
Lee, Jun Hee ;
Jung, Jin Sup ;
Noh, Hyunjin ;
Baek, Moo Jun ;
Ryu, Jung Min ;
Yoon, Yeo Min ;
Han, Ho Jae ;
Lee, Sang Hun .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 2015, 198 :187-195