Abstract
BackgroundIn former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively.MethodsMSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated.ResultsIn grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression.ConclusionsOur results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.
Highlights
In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft
Characterization of rat MSC As detailed elsewhere the MSC used in the present study were isolated from Sprague Dawley Enhanced Green Fluorescent Protein (EGFP) rats and differentiated into osteogenic and adipogenic cells
Tissue and serum levels of cytokines The expression in renal tissue of IFN-γ, IL-10, IL-6, IL2, IL-1 was significantly increased in grafted kidneys not injected with MSC compared with native kidneys
Summary
In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. In a rat model of kidney transplantation we found that MSC injected in the graft improved its function and attenuated renal injury, reducing significantly tubulitis, vasculitis, glomerulitis and has been given that MSC modify the cytokine network in the setting of renal graft, so that we have felt it interesting to test the hypothesis in the present study. The Scatter Factor (SF) system consists of Hepatocyte Growth Factor (HGF) and Macrophage Stimulating Protein (MSP) and their receptors Met and RON respectively. We demonstrated that in experimental anti Thy-1 nephritis MSC improve renal injury by modulating SFs [43]
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