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

Figure 6

Repair effect of engineered MSC-Exos on ischemic heart. Exosomes secreted by bone marrow mesenchymal stem cells (BMMSCs) preconditioned with moderate hypoxia promote angiogenesis or anti-myocardial apoptosis through upregulation of miR-24, miR-125b-5p, miR-210, HMGB1, etc. HIF-1α-overexpressing mesenchymal stem cells (MSCs) secreted exosomes (Exo-HIF-1α), SDF1-overexpressing human umbilical cord mesenchymal stem cells (hUCMSCs) secreted exosomes (Exo-SDF1), CXCR4-overexpressing bone marrow mesenchymal stem cells (BMMSCs) secreted exosomes (Exo-CXCR4), TIMP2-modified hUCMSCs secreted exosomes (Exo-TIMP2), and MIF-overexpressing hUCMSCs secreted exosomes (Exo-MIF), AKT-modified hUCMSCs secreted exosomes (Exo-AKT), and GATA-4 overexpressing BMMSCs secreted exosomes (Exo-GATA-4), atorvastatin pretreated BMMSCs secreted exosomes (ATV-Exo), hemin pretreated BMMSCs secreted exosomes (Hemin-Exo) played a better role in promoting angiogenesis or antimyocardial apoptosis in infarcted hearts. HMGB1, high mobilitygroup box 1 protein; SDF1, stromal-derived factor 1; Bax, Bcl-2-associated X protein; Bcl-2, B-Cell CLL/Lymphoma 2; MMP-2, matrix metalloprotein-2; MMP-9, matrix metalloprotein-9; VEGF, vascular endothelial growth factor; AKT, protein kinase B; PDGF-D, platelet-derived growth factor D; HIF-1α, hypoxia-inducible factor 1α; IGF-1α, insulin-like growth factor-1α; MIF, macrophage migration inhibitory factor; Sfrp2, secreted frizzled-related protein 2; TIMP2, recombinant tissue inhibitors of metalloproteinase 2; GATA-4, GATA binding protein 4; ATV, atorvastatin.