The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms' tumor protein antibody characteristics of Wilms' tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms' tumor development.
Electronic poster abstractsConclusions: The clinical pregnancy rate found to be high in Hycosy with new contrast group, when compared to non-flushing group.
Background: Trafficking of regulatory T cells (Tregs) modulate inflammatory response after kidney transplantation. There is scarce information on whether circulating and intragraft Tregs are similarly affected by immunosuppressive drugs (ISD) and by the type of deceased kidney donor.Objectives: 1-to study the simultaneous gene and protein expression of the FOXP3 (forkhead-winged helix transcription factor) in the peripheral blood (PB) and within renal allografts; 2-to correlate FOXP3 expression with the immunosuppressive drugs (ISD) used and kidney donor type. Methods: FOXP3 gene and protein expression were assessed by real-time PCR and immunohistochemical analysis in the peripheral blood (PB) and kidney biopsies (Bx) of patients receiving Tacrolimus (Tac; n=21) or Everolimus (Eve; n=19) at the 3rd month post-Tx. FOXP3 expression was correlated with donor type (standard -SCD or extended criteria -ECD donors), ISD, acute rejection (AR), delayed graft function (DGF), and serum creatinine (sCr) at one year. Results: Eve-treated patients had a longer DGF duration (p=0.04) and a lower frequency of de novo post-Tx diabetes (p=0.03) compared with the Tac group. FOXP3 expression in the PB and Bx was greater in Eve than in Tac-treated patients. Immunohistochemistry did not show differences in the FOXP3 expression for both types of ISD. Recipients of SCD and ECD had similar gene and protein expression inside allografts and in the renal tissue regardless of the ISD. However, in the PB, ECD recipients treated with Eve (ECD/Eve) had higher FOXP3 expression than ECD/Tac (p=0.04) and SCD/Eve (p= 0.01). In the blood Eve and ECD kidney (OR= 5.6; p= 0.04 and OR= 8.7; p= 0,015, respectively) were independently associated with FOXP3 expression while in the Bx only Eve was associate with increased gene expression (OR=5.1; p= 0.03). Conclusion: FOXP3 gene and protein expression does occur differently in the blood and inside allografts from recipients of ECD kidneys treated with mTOR inhibitors. We suggest caution when interpreting studies comparing outcomes based on the measurement of the FOXP3 gene expression in different tissues and compartments and kidney donor types.
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