Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity
SourceExperimental and Toxicologic Pathology, 65, 5, (2013), pp. 595-600
Article / Letter to editor
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Paediatrics - OUD tm 2017
Experimental and Toxicologic Pathology
SubjectIGMD 9: Renal disorder; NCMLS 3: Tissue engineering and pathology; NCMLS 5: Membrane transport and intracellular motility IGMD 9: Renal disorder
Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0-3000mug/ml gentamicin for 24h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000mug/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500-3000mug/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity.
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