title: Effect of preemptive treatment with human umbilical cord blood-derived mesenchymal stem cells on the development of renal ischemia-reperfusion injury in mice.
abstract: Human umbilical cord blood-derived mesenchymal 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- to 10-wk-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed, and 1 × 10(6) HUCB-MSCs were injected intraperitoneally 24 h before 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 after IRI were attenuated by HUCB-MSC treatment. PKH-26-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-γ in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal VEGF after 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 natural killer T cells and increased number of regulatory T cells in postischemic kidneys. In addition, these effects of HUCB-MSCs on kidney infiltrating mononuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase after IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI.
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea;
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea;
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pathology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea; and.
authors.forename: Ghee Young
authors.initials: GY
authors.lastname: Kwon
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea;
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea;
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.affiliation: Biomedical Research Institute, MEDIPOST Company Limited, Seoul, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Biomedical Research Institute, MEDIPOST Company Limited, Seoul, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Biomedical Research Institute, MEDIPOST Company Limited, Seoul, Korea.
authors.forename: Wonil
authors.initials: W
authors.lastname: Oh
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea;
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Oh
authors.affiliation: Nephrology Division, Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea; ygkim26@skku.edu.
authors.forename: Yoon-Goo
authors.initials: YG
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma
keywords: human umbilical cord blood-derived mesenchymal stem cells; inflammation; mesenchymal stem cells; renal ischemia-reperfusion injury