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

• DOI: 10.1186/s12951-021-00808-5
• Publication Date: 2021-02-27T17:03:11Z
• Authors: Wenwu Zhu; Ling Sun; Pengcheng Zhao; Yaowu Liu; Jian Zhang; Yuelin Zhang; Yimei Hong; Yeqian Zhu; Yao Lu; Wei Zhao; Xinguang Chen; Fengxiang Zhang
• Keywords: Exosome; Cardioprotection

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