Investigation of the effects of bone marrow-derived mesenchymal stem cells in the chronic cyclosporine nephrotoxicity

Cyclosporine A (CsA) is a powerful immunosupressant which is used for allogenic transplantation and nephrotic syndrome treatment. Idiosychratic chronic nephrotoxicity is the most important side effect limiting use of CsA. Mesenchymal stem cells are often used because they have the advantage of being able to be used autologous, not causing ethical problems and being able to be got from more sources. In this study the aim was to evaluate the effects of experimental mesenchymal stem cells on chronic CsA nephrotoxicity.In this study 40 young adult Wistar rats were included. Rats in the group 1 had 15mg/kg/d subcutaneous cyclosporine for 60 days. Rats in the group 2 had cyclosporine by the same way and 60 days later were administered bone marrow derived mesenchymal stem cells. Rats in the group 3 had only bone marrow derived mesenchymal stem cells. Rats in the Group 4 were controls. All the rats were sacrified at the end of the 67. day and all the renal tissues were examined histologically and immunohistochemically (TGF-ß1, TGF-ß3, Collagen-1, Brd-U, CD4).Arteriolopathy and tubular atrophy in group 2 were less than group 1. Increase in tubulointerstitial mononuclear cells was higher in both group 1 and 2 compared to other two groups, but there were no significant difference between group 1 and 2. This was thought to be due to inflammatory cells infiltrating tubulointerstitial area caused by CsA and/or mesenchymal stem cells migrating here. Increase in positive marking with Brd-U staining supports our thought of some of these cells were administered mesenchymal stem cells. We suggested mesenchymal stem cells contributed to tubuler regeneration following migration to injured area. In group 3 and 4 there was no finding suggesting tubular atrophy, fibrosis and arteriolopathy. Immunohistochemically, in group 2, staining with TGF-ß1 and TGF-ß3 were significantly decreased compared to group 1. This in turn was showing favorable effects of mesenchymal stem cells on tubulointerstitial fibrosis.In conclusion, we showed that histopathologic findings caused by experimental chronic CsA nephrotoxicity can be reversed by bone marrow-derived mesenchymal stem cells