Review Article

Mechanisms and Optimization Strategies of Paracrine Exosomes from Mesenchymal Stem Cells in Ischemic Heart Disease

Figure 5

Exosomes secreted by different sources of MSCs regulate the inflammatory microenvironment after myocardial infarction. (a) MiR-200b-3p in extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) inhibits the activation of NLRP1 by inhibiting the expression of Bcl-2-like protein 11 (Bcl2L11), which effectively inhibits the inflammatory response after myocardial infarction (MI). MiR-302d-3p in EVs derived from bone marrow mesenchymal stem cells (BMMSCs) regulates the post-MI inflammatory microenvironment by mediating the BCL6/MD2/NF-κB axis. MiR-25-3p in exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) inhibits the inflammatory response of ischemic myocardial injury by downregulating enhancer of zest homolog 2 (EZH2) and inhibiting suppressor of cytokine signaling 3 (SOCS3) expression. (b) BMMSC-Exos regulate the postinfarction cardiac microenvironment by upregulating p27kip1 and downregulating CDK2 to inhibit the proliferation of CD3+ T cells after MI and inhibit the proliferation and differentiation of B cells. MiR-181a in exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-Exos) can significantly inhibit the inflammatory response and increase the proportion of Treg cells by targeting the inflammatory transcription factor c-fos, thereby inhibiting T-cell proliferation. (c) MiR-182 in BMMSC-Exos targets the TLR4/NF-κB/PI3K/AKT signaling cascade to promote M1-to-M2 polarization of macrophages. Meanwhile, BMMSC-Exos can promote macrophage differentiation to the M2 phenotype through miR-21-5p, thereby reducing inflammation. Exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exos) promote macrophage M2 polarization and cardiac repair by activating S1P/SK1/S1PR1 signal transduction. BMMSC-Exos overexpressing fibronectin type III domain-containing protein 5 (FNDC5) play an anti-inflammatory role by inhibiting the NF-κB signaling pathway and promoting the polarization of M2 macrophages.
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