Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-inflammation and restoring gut dysbiosis

Abstract

Background Myocardial infarction (MI) represents a severe cardiovascular disease with limited therapeutic agents. This study was aimed to elucidate the role of the exosomes derived from human placental mesenchymal stem cells (PMSCs-Exos) in MI. Methods PMSCs were isolated and cultured in vitro, with identification by both transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). To further investigate the effects of PMSC-Exos on MI, C57BL/6 mice were randomly divided into Sham group, MI group, and PMSC-Exos group. After 4 weeks of the intervention, cardiac function was assessed by cardiac echocardiography, electrocardiogram and masson trichrome staining; lipid indicators were determined by automatic biochemical instrument; inflammatory cytokines were measured by cytometric bead array (CBA); gut microbiota, microbial metabolites short chain fatty acids (SCFAs) as well as lipopolysaccharide (LPS) were separately investigated by 16S rRNA high throughput sequencing, gas chromatography mass spectrometry (GC–MS) and tachypleus amebocyte lysate kit; transcriptome analysis was used to test the transcriptional components (mRNA\miRNA\cirRNA\lncRNA) of PMSC-Exos. Results We found that human PMSC-Exos were obtained and identified with high purity and uniformity. MI model was successfully established. Compared to MI group, PMSC-Exos treatment ameliorated myocardial fibrosis and left ventricular (LV) remodeling (P < 0.05). Moreover, PMSC-Exos treatment obviously decreased MI molecular markers (AST/BNP/MYO/Tn-I/TC), pro-inflammatory indicators (IL-1β, IL-6, TNF-α, MCP-1), as well as increased HDL in comparison with MI group (all P < 0.05). Intriguingly, PMSC-Exos intervention notably modulated gut microbial community via increasing the relative abundances of Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Akkermansia, Bacteroides, Bifidobacterium, Thauera and Ruminiclostridium, as well as decreasing Firmicutes (all P < 0.05), compared with MI group. Furthermore, PMSC-Exos supplementation increased gut microbiota metabolites SCFAs (butyric acid, isobutyric acid and valeric acid) and decreased LPS in comparison with MI group (all P < 0.05). Correlation analysis indicated close correlations among gut microbiota, microbial SCFAs and inflammation in MI. Conclusions Our study highlighted that PMSC-Exos intervention alleviated MI via modulating gut microbiota and suppressing inflammation.

Dietary Modulation of the Human Gut Microbiota and Metabolome with Flaxseed Preparations

“…After 18 h, Firmicutes and the genus Acidaminococcus showed the highest relative abundance. Increases in the genus Acidaminococcus , belonging to the phylum Firmicutes, has been associated with acute myocardial infarction and the flaxseed oil supplementation of lambs’ diet [ 35 , 36 , 37 ].…”

Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases

“…Numerous studies have shown that exosomes secreted by varieties of immune cells (DCs, macrophages, neutrophils) and non-immune cells (MSCs, platelets) participate in the occurrence and development of chronic inflammation [ 70 , 71 ], and play an important role in regulating the inflammatory microenvironment by regulating gene expression and releasing anti-inflammatory factors ( Fig. 4 ) [ 72 , 73 ]. More importantly, in recent years, exosomes have attracted attention as optimal drug carriers for personalized nanomedicine due to their high biocompatibility, low immunogenicity, and ability to inherit many characteristics of parental cells [74] .…”

Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases

“…Death of many cardiomyocytes causes strong inflammation after MI, and studies have shown that intestinal microflora participates in the occurrence of this kind of inflammation ( Wang et al, 2018 ; Zununi Vahed et al, 2018 ). ( Yang et al, 2022 ) pointed out that PMSCs-Exo shows angiogenesis and anti-inflammatory potential in the cell therapy of MI and regulates the intestinal microflora. Gene ontology enrichment analysis of the PMSCs-Exo-lncRNA target gene revealed that lncRNA performs numerous functions at the transcriptional level, suggesting that PMSCs-Exo-lncRNA is a potential target for MI therapy.…”