Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence

• DOI: 10.1186/s12951-021-01077-y
• Publication Date: 2021-10-21T12:02:36Z
• Authors: Huifeng Zheng; Xiaoting Liang; Qian Han; Zhuang Shao; Yuxiao Zhang; Linli Shi; Yimei Hong; Weifeng Li; Cong Mai; Qingwen Mo; Qingling Fu; Xiaoxue Ma; Fang Lin; Mimi Li; Bei Hu; Xin Li; Yuelin Zhang
• Keywords: Hemin; Senescence

Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects MSCs in mouse model MI. This aimed to investigate EXO derived from hemin-pretreated (Hemin-MSC-EXO) MI and explore potential mechanisms.MSC-EXO Hemin-MSC-EXO were collected characterized. MSC-EXO intramuscularly injected into peri-infarct region Heart function mice was assessed by echocardiography. The mitochondrial morphology neonatal cardiomyocytes (NMCMs) under serum deprivation hypoxic (SD/H) conditions examined Mitotracker staining. cellular senescence NMCMs determined senescence-associated-β-galactosidase assay. A loss-of-function approach adopted determine role Hemin-MSC-exosomal-miR-183-5p regulation cardiomyocyte RESULTS: successfully isolated supernatant Hemin-pretreated MSCs. Compared MSC-EXO, injection significantly improved cardiac reduced fibrosis. Both ameliorated fission vitro vivo, latter exhibited better protective effects. MicroRNA sequencing revealed higher level miR-183-5p than MSC-EXO. MiR-183-5p knockdown partially abrogated attenuating induced SD/H. High mobility group box-1 (HMGB1) abundance lower Hemin-MSC-EXO-treated MSC-EXO-treated hearts, HMGB1 identified one target genes miR-183-5p. Mechanistically, inhibited SD/H-induced delivering recipient via HMGB1/ERK pathway. Furthermore, Hemin-MSC-EXO-mediated MI.Our results reveal are superior treating Exosomal mediates, at least partially, inhibiting highlights have high translational value repairing dysfunction following infarction.