Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction

Figure 8

Schematic depiction of functional exosomes secreted from MSC overexpressing CXCR4 for activation of signaling pathways for restoration of LV function after MI. In exosome generating cells, CXCR4 are selectively incorporated into the intraluminal vesicles (IVLs) of multivesicular endosomes (MVEs) from the plasma membrane. Then, by fusing with the plasma membrane, MVEs release CXCR4-enriched exosome into the extracellular milieu. CXCR4-enriched exosomes can bind to the plasma membrane of the targeting cells. These recruited CXCR4-enriched exosomes may either fuse directly with the plasma membrane or fuse with delimiting membrane of an endocytic compartment. Then, released CXCR4 can be delivered into the membrane or cytosol of the targeting cell which contributes to SDF-1α/CXCR4 interaction. In infarcted heart tissue, increased binding of SDF-1α to CXCR4 activates G-protein-coupled receptor kinases, which activate a cascade of signaling pathways in cells. Pretreatment of stem/progenitor cells with CXCR4-enriched exosome can reduce MI-induced cell death and promote angiogenesis through PI3K/Akt signaling pathway activation, thereby enhancing heart function improvement.