Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7

Abstract

It has been previously reported that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC)‑exosomes exhibit cardioprotective effects on the rat acute myocardial infarction (AMI) models and cardiomyocyte hypoxia injury models in vitro, however the exact mechanisms involved require further investigation. The present study aimed to investigate the repair effects of hucMSC‑exosomes on myocardial injury via the regulation of mothers against decapentaplegic homolog 7 (Smad7) expression. Compared with sham or normoxia groups (in vivo and in vitro, respectively), western blotting demonstrated that Smad7 expression was significantly decreased in the borderline area of infraction myocardium and in H9C2(2‑1) cells following hypoxia‑induced injury. Additionally, microRNA (miR)‑125b‑5p expression was markedly increased using reverse transcription‑quantitative polymerase chain reaction, but was reversed by hucMSC‑exosomes. Trypan blue staining and lactate dehydrogenase release detection demonstrated that cell injury was significantly increased in the AMI + PBS and hypoxia group compared with in the sham and normoxia groups and was inhibited by hucMSC‑exosomes. A dual luciferase reporter gene assay confirmed that Smad7 is a target gene of miR‑125b‑5p. In addition, miR‑125b‑5p mimics promoted H9C2(2‑1) cell injury following 48 h exposure to hypoxia. Downregulation of Smad7 expression under hypoxia was increased by miR‑125b‑5p mimics compared with the mimic negative control, and hucMSC‑exosomes partially alleviated this phenomenon. In conclusion, hucMSC‑exosomes may promote Smad7 expression by inhibiting miR‑125b‑5p to increase myocardial repair. The present study may provide a potential therapeutic approach to improve myocardial repair following AMI.

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

“…In recent years, increasing studies provided strong evidence that MSC-Exos involve in damage repair process by delivering functional proteins or RNAs. For example, Wang et al [24] showed that exosomes derived from human umbilical cord MSCs improved myocardial repair via Smad7 upregulation. Tao et al [25] observed that exosomes derived from miR-140-5p-overexpressing synovial MSCs promoted the proliferation and migration of rat chondrocytes, which in turn ameliorated OA.…”

Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway

“…Exosomes are cell-derived vesicles that transport proteins, lipids, DNA, and RNA and are involved in signal transduction, immune responses, antigen presentation, and would healing among other cellular processes [11], indicating their potential in bioactive therapies. In fact, hucMSC-derived exosomes have been shown to exert cardioprotective effects [12, 13].…”

Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

“…UC-MSC-EVs have also been indicated to provide pro-proliferative effect in cells residing in border zone area of infarcted myocardium, as shown in rat models of AMI in vivo by increased level of Ki67 indicating cardiac cell proliferation [53]. A study conducted by Wang et al revealed that EVs from UC-MSCs enhance Smad7 expression via inhibiting its impeditory miR-125b-5p, which eventually resulted in decline in myocardial cells apoptosis and injury [54]. Interestingly, study from Liu and colleagues suggests that UC-MSC-EVs may also regulate autophagy in cardiac cells by activating PI3K/AKT/mTOR signaling pathway leading to inhibition of heart cells apoptosis in rat model [55].…”