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

Figure 4

Angiogenic effect of exosomes released by different MSCs after MI. Exosomes derived from umbilical cord mesenchymal stem cells (UCMSCs), adipose-derived mesenchymal stem cells (ADMSCs), and bone marrow mesenchymal stem cells (BMMSCs) promote angiogenesis by increasing levels of hepatocyte growth factor (HGF), angiogenic fibroblast growth factor-β (FGF-β), and vascular endothelial growth factor (VEGF). Exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exos) can upregulate the expression of the angiogenic genes Ang1 (also known as ANGPT1) and Flk1 (also known as KDR) and downregulate the expression of the antiangiogenic genes Vash1 and TSP1 (also known as THBS1). Human amniotic fluid exosomes derived from mesenchymal stem cells (MSC-Exos) promote angiogenesis by increasing the expression of HIF-1α and VEGF in fibrotic hearts. Exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) increase capillary density and blood flow in ischemic myocardial tissue by upregulating the MAPK and AKT/eNOS pathways. Extracellular vesicles (EVs) secreted by BMMSCs can promote the angiogenesis of infarcted hearts by regulating the miR-210-Efna3 pathway. MiR-132 mimics and miR-29b-3p loaded in BMMSC-Exos significantly promote neovasculature around the infarcted heart by regulating RASAI gene expression and A Disintegrin and Metalloproteinase with Thrombospondin Motifs 16 (ADAMTS16) expression, respectively. MiR-125a and miR-31 in ADMSC-Exos promote endothelial cell angiogenesis by inhibiting the expression of the angiogenic inhibitor delta-like 4 (DLL4) and activating the FIH1/HIF-1α pathways, respectively. MiR-543 in human MSC-Exos promotes the formation of cardiac microvascular endothelial cells by downregulating the expression of COL4A1. miR-1246 in exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exos) promotes angiogenesis by targeting the PRSS23/Snail/α-SMA axis.