Effect of preemptive treatment with human umbilical cord blood-derived mesenchymal stem cells on the development of renal ischemia-reperfusion injury in mice.

American Journal of Physiology, Renal Physiology

PubMedID: 25143451

Jang HR, Park JH, Kwon GY, Lee JE, Huh W, Jin HJ, Choi SJ, Oh W, Oh HY, Kim YG. Effect of preemptive treatment with human umbilical cord blood-derived mesenchymal stem cells on the development of renal ischemia-reperfusion injury in mice. Am J Physiol Renal Physiol. 2014;307(10):F1149-61.
Human umbilical cord blood-derived stem cells (HUCB-MSCs) have been studied in several models of immune-mediated disease because of their unique immunomodulatory properties. We hypothesized that HUCB-MSCs could suppress the inflammatory response in postischemic kidneys and attenuate early renal injury. In 8-10-week-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed and 1x106 HUCB-MSCs were injected intraperitoneally 24 h prior to surgery and during reperfusion. Renal functional and histological changes, HUCB-MSC trafficking, leukocyte infiltration, and cytokine expression were analyzed. Renal functional decline and tubular injury following IRI were attenuated by HUCB-MSC treatment. PKH26-labeled HUCB-MSCs trafficked into the postischemic kidney. Although numbers of CD45-positive leukocytes in the postischemic kidney were comparable between groups, the expression of interferon-? in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal vascular endothelial growth factor (VEGF) following IRI was markedly mitigated by HUCB-MSC treatment. In inflammatory conditions simulated in a cell-culture experiment, VEGF secretion from HUCB-MSCs was substantially enhanced. VEGF inhibitor abolished the renoprotective effect of HUCB-MSCs after IRI. Flow cytometry analysis revealed the decreased infiltration of NKT cells and increased number of regulatory T cells in the postischemic kidneys. And, these effects of HUCB-MSCs on the kidney infiltrating mononuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase following IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI.