Macrophage migration inhibitory factor facilitates the therapeutic efficacy of mesenchymal stem cells derived exosomes in acute myocardial infarction through upregulating miR-133a-3p

Journal of Nanobiotechnology

Yaowu Liu¹  Yimei Hong²  Yuelin Zhang²  Yao Lu³  Wenwu Zhu³  Pengcheng Zhao³  Yeqian Zhu³  Wei Zhao³  Fengxiang Zhang³  Xinguang Chen³  Jian Zhang³  Ling Sun⁴ 

[1] Department of Cardiology, Zhongda Hospital of Southeast University, Nanjing, China;Department of Emergency and Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, Guangzhou Road 300, 210029, Nanjing, People’s Republic of China;Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, Guangzhou Road 300, 210029, Nanjing, People’s Republic of China;Department of Cardiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China;

关键词: Exosomes;    Macrophage migration inhibitory factor;    UcMSCs;    MiR-133a-3p;    Myocardial infarction;   

DOI  :  10.1186/s12951-021-00808-5

来源: Springer

【 摘 要 】

BackgroundExosome transplantation is a promising cell-free therapeutic approach for the treatment of ischemic heart disease. The purpose of this study was to explore whether exosomes derived from Macrophage migration inhibitory factor (MIF) engineered umbilical cord MSCs (ucMSCs) exhibit superior cardioprotective effects in a rat model of AMI and reveal the mechanisms underlying it.ResultsExosomes isolated from ucMSCs (MSC-Exo), MIF engineered ucMSCs (MIF-Exo) and MIF downregulated ucMSCs (siMIF-Exo) were used to investigate cellular protective function in human umbilical vein endothelial cells (HUVECs) and H9C2 cardiomyocytes under hypoxia and serum deprivation (H/SD) and infarcted hearts in rats. Compared with MSC-Exo and siMIF-Exo, MIF-Exo significantly enhanced proliferation, migration, and angiogenesis of HUVECs and inhibited H9C2 cardiomyocyte apoptosis under H/SD in vitro. MIF-Exo also significantly inhibited cardiomyocyte apoptosis, reduced fibrotic area, and improved cardiac function as measured by echocardiography in infarcted rats in vivo. Exosomal miRNAs sequencing and qRT-PCR confirmed miRNA-133a-3p significantly increased in MIF-Exo. The biological effects of HUVECs and H9C2 cardiomyocytes were attenuated with incubation of MIF-Exo and miR-133a-3p inhibitors. These effects were accentuated with incubation of siMIF-Exo and miR-133a-3p mimics that increased the phosphorylation of AKT protein in these cells.ConclusionMIF-Exo can provide cardioprotective effects by promoting angiogenesis, inhibiting apoptosis, reducing fibrosis, and preserving heart function in vitro and in vivo. The mechanism in the biological activities of MIF-Exo involves miR-133a-3p and the downstream AKT signaling pathway.

【 授权许可】

CC BY