The Role of Human Cord Blood Endothelial Colony Forming Cell-Derived Extracellular Vesicles In Acute Kidney Injury (AKI)

Abstract

Acute kidney injury (AKI) is a sudden reduction in renal function, associated with a high mortality rate. The main cause of AKI is ischemia reperfusion injury. We previously found that administration of endothelial colony forming cells (ECFCs) or their derived exosomes protects ischemic renal cells against ischemia via paracrine action. Moreover, ECFC-derived exosomes are highly enriched with miRNA-486-5p, which protects against ischemia. Unexpectedly, ECFC infusion into mice with AKI attenuates renal endothelial cell proliferation. Therefore, we examined the role of ECFC-derived exosomes and microparticles (MPs) on endothelial cell angiogenic properties (proliferation and migration) in vitro, the pathways by which exosomes get internalized into endothelial cells, and the effects of miRNA-486-5p on endothelial cell migration. Results: ECFC-derived exosomes and MPs enhance endothelial cell proliferation in hypoxia and normoxia, and improve cellular migration. Finally, miRNA-486-5p plays a role in inducing HUVEC migration in normoxia. Conclusion: These findings indicate that ECFC-derived exosomes and MPs protect endothelial cells against ischemia by activating cellular migration, and that miRNA-486-5p plays a role in endothelial cell recovery after ischemia.