Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages
Renal stem cell
DOI:
10.1186/scrt469
Publication Date:
2014-06-24T09:08:03Z
AUTHORS (11)
ABSTRACT
Abstract Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects macrophage activation therapy AKI. Methods MSCs were injected into glycerol-induced rhabdomyolysis mice. Renal evaluated using serum creatinine, urea nitrogen, renal pathology and tubular necrosis score. distribution detected two-photon fluorescence confocal imaging. Immunofluorescence anti-F4/80 anti-CD206 performed determine macrophages tissues kidney, infiltration also western blotting analyses. After depletion clodronate liposomes at phase repair, re-evaluated. RAW 264.7 incubated with lipopolysaccharide co-cultured subsequently visualised immunofluorescence staining flow cytometry analysis. Finally, disparate phenotype including normal (M0), lipopolysaccharide-stimulated (M1), MSC-co-cultured (M2), infused mice AKI, pre-treated liposomal clodronate. Results In vivo infusion protected AKI from function impairment severe injury, accompanied by a time-dependent increase CD206-positive infiltration. addition, depleting delayed restoration vitro , acquired an anti-inflammatory phenotype, characterised increased expression CD206 secretory cytokine interleukin (IL)-10. concentrations IL-10, IL-6 tumor factor α enzyme-linked immunosorbent assay. Furthermore, macrophage-depleted intramuscular injection glycerol subjected single different types macrophages. Mice M0 M1 suffered more histological functional while transfused MSC-educated showed reduced Conclusions Our findings suggested ameliorate via trophic supports transition tubule repair.
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