The Anti-Oxidative Role of Micro-Vesicles Derived from Human Wharton-Jelly Mesenchymal Stromal Cells through NOX2/gp91(phox) Suppression in Alleviating Renal Ischemia-Reperfusion Injury in Rats

Oxidative stress is known as one of the main contributors in renal ischemia/reperfusion injury (IRI). Here we hypothesized that Micro-vesicles (MVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) could protect kidney against IRI through mitigating oxidative stress. MVs isolated from hWJMSCs conditioned medium were injected intravenously in rats immediately after unilateral kidney ischemia for 60 min. The animals were sacrificed at 24 h, 48 h and 2 weeks respectively after reperfusion. Our results show that the expression of NOX2 and reactive oxygen species (ROS) in injured kidney tissues was declined and the oxidative stress was alleviated in MVs group at 24 h and 48 h in parallel with the reduced apoptosis and enhanced proliferation of cells. IRI-initiated fibrosis was abrogated by MVs coincident with renal function amelioration at 2 weeks. NOX2 was also found down-regulated by MVs both in human umbilical vein endothelial cells (HUVEC) and NRK-52E cell line under hypoxia injury model in vitro. In conclusion, a single administration of hWJMSC-MVs might protect the kidney by alleviation of the oxidative stress in the early stage of kidney IRI through suppressing NOX2 expression. Moreover, it could reduce the fibrosis and improved renal function.