The effect of induced mesenchymal stem cells on podocyte injury model

Self-renewal, multipotent, immunomodulating properties and low rejection risk of mesenchymal stem cell (MSC) render it to be an important therapeutic option in severe diseases such as Focal Segmental Glomerulosclerosis (FSGS). Remission of FSGS after treatment with corticosteroids and other immunosuppressive drugs can be achieved only partially and progression to kidney failure due to podocyte damage is likely. In those patients who have had a kidney transplant due to end-stage renal disease, recurrence of the disease may occur. The aim of this thesis was to investigate the effect of MSCs primed by insulin growth factor-1 and hepatocyte growth factor (IGF-1+HGF_MSC) in in vitro and in vivo podocyte damage models induced by puromycin aminonucloside (PAN) to test the hypothesis that IGF-1 and HGF priming would enhance the therapeutic effect of MSCs. Firstly, detailed characterization of IGF-1+HGF_MSC was performed. IGF-1+HGF_MSC does not express tumorogenity related markers CD200, CD271, CD184/CXCR4, SSEA4 similar to conventional MSCs. In vitro scratch assay revealed that IGF-1+HGF_MSC showed faster closure of the wound area. Increase in the expression of IDO-1 and TGF-β, and in the secretion of IL-6, MCP-1, angiogenin and picolinic acid metabolite of the IGF-1+HGF_MSC group compared to conventional MSCs were observed. Co-culture assays revealed that IGF-1+HGF_MSC ameliorated the impaired podocyte actin cytoskeleton structure and caused an increase in the expression of INF2 gene. It was determined that the administration of IGF-1+HGF_MSC reduced proteinuria in the in vivo rat FSGS model better than the conventional MSCs and reversed the loss of slit diaphragm.