Bone marrow mesenchymal stem cell‑derived exosomes protect against myocardial infarction by promoting autophagy

Abstract

Exosomes have been demonstrated to be effective in the treatment of a variety of cardiac disorders. However, the effects of mesenchymal stem cell (MSC) exosomes on myocardial infarction is yet to be determined. The current study aimed to investigate the potential therapeutic effects of MSC exosomes on myocardial injuries that are caused by myocardial infarction. MSCs were isolated from rat bone marrow and were used for exosome enrichment using culture medium. Confirmation that MSCs and exosomes had been successfully extracted was performed using flow cytometry, electron microscopy and western blot analysis. A rat myocardial ischemia reperfusion (I/R) model was established by ligation of the left anterior descending coronary artery. Rat myocardial injuries were determined using 2,3,5-triphenyltetrazolium chloride, Masson and TUNEL staining. H9c2 cell proliferation, apoptosis and migration were analyzed using 5-ethynyl-2′-deoxyuridine, Hoechst staining, flow cytometry and Transwell assays. Marker gene expression was evaluated using reverse transcription-quantitative PCR, western blot analysis and immunofluorescence. Rat MSC exosomes were revealed to suppress myocardial injury and the myocardiocyte functions that were induced by I/R. The results also demonstrated decreased apoptotic protease activating factor-1 and increased autophagy-related protein 13 expression. The H9c2 cell proliferation and migration inhibition, as well as cell apoptosis during hypoxia-reoxygenation (H/R), were suppressed by rat MSC exosomes, with an alteration of the expression of apoptotic and autophagic genes also being demonstrated. The application of autophagy inhibitor 3-methyladenine significantly mitigated the effect of exosomes on H9c2 cell proliferation and apoptosis, which were induced by H/R. Rat MSC exosomes inhibited myocardial infarction pathogenesis, possibly by regulating autophagy.

Exosomes Secreted From Bone Marrow Mesenchymal Stem Cells Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Pyroptosis in PC12 Cells by Promoting AMPK-Dependent Autophagic Flux

“…Autophagy is a dynamic process of degradation (Cardinal et al, 2009 ). The protective effect of BMSC-Exos on myocardial I/R injury appears to be closely related to the activation of autophagy (Zou et al, 2019 ), but their mechanism of autophagy in cerebral I/R injury has never been reported. In the current study, both the results of TEM and GFP-RFP-LC3 indicated that there was a large increase in number of autolysosomes in the OGD/R+BMSC-Exos group, further suggesting that BMSC-Exos was involved in the promotion of autophagic flux.…”

“…Moreover, without any cytological characteristics such as proliferation and differentiation of BMSCs, BMSC-Exos have relatively stable biological characteristics, which reduce the risk of BMSC transplantation and make it possible to replace BMSCs for more effective treatment of cerebral I/R injury. In addition, BMSC-Exos have been shown to protect against myocardial I/R injury and inhibit myocardial infarction pathogenesis by regulating autophagy (Zou et al, 2019 ). Therefore, we hypothesized that BMSC-Exos may have a similar effect in cerebral I/R injury and the mechanism may be related to autophagy and pyroptosis.…”

Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo

“…MSC-derived EVs are reported to have a therapeutic effect in a broad spectrum of diseases. Beneficial effects in ischemia-reperfusion induced kidney injury [102] and protective properties against myocardial infarction [103]; just two of many examples demonstrating their therapeutic potential. These EVs contain a specific enriched subset of miRNAs [104] and proteins [105], modulating cellular response and triggering tissue repair [106].…”

Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis

“…The main sources are the bone marrow MSCs (BM-MSCs), adipose-derived MSCs (AD-MSCs), and umbilical cord MSCs (UC-MSCs). A large number of studies have investigated the role of MSCs in many diseases, including diabetic retinopathy [12], myocardial infarction [13], diabetes [14], and DN [15][16][17][18][19] in mice and rats. However, the underlying mechanisms of these beneficial effects are not completely elucidated.…”