Micro‐vesicles derived from human Wharton's Jelly mesenchymal stromal cells mitigate renal ischemia‐reperfusion injury in rats after cardiac death renal transplantation

Abstract The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton‐Jelly mesenchymal stromal cells derived micro‐vesicles (hWJMSCs‐MVs) on renal ischemia‐reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post‐transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)‐α, and interleukin (IL)‐10 levels in the serum. Tubular cell proliferation and apoptosis were identified by Ki67 immunostaining and TUNEL assay. Renal fibrosis was assessed by Masson's tri‐chrome straining and alpha‐smooth muscle actin (α‐SMA) staining. The infiltration of inflammatory cells was detected by CD68 + staining. The transforming growth factor (TGF)‐β, hepatocyte growth factor (HGF), and α‐SMA expression in the kidney was measured by Western blot. After renal transplantation, the rats treated with hWJMSCs‐MVs improved survival rate and renal function. Moreover, MVs mitigated renal cell apoptosis, enhanced proliferation, and alleviated inflammation at the first 48 h. In the late period, abrogation of renal fibrosis was observed in the MVs group. MVs also could decrease the number of CD68 + macrophages in the kidney. Furthermore, MVs decreased the protein expression levels of α‐SMA and TGF‐β1 and increased the protein expression level of HGF at any point (24 h, 48 h, 1 or 2 weeks). The administration of MVs immediately after renal transplantation could ameliorate IRI in both the acute and chronic stage.