Abstract

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.

Highlights

  • Treatments available for chronic kidney disease (CKD), dialysis, and renal transplantation have many drawbacks [1]

  • We previously showed that rats with CKD treated with bone marrow-derived mesenchymal stem cells (BMSCs) injected into the renal parenchyma did stabilize the progression of disease [2]

  • Bone marrow-derived BMSCs from rats which showed stable fibroblast-like phenotypes in culture were isolated by adherence separation

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Summary

Introduction

Treatments available for chronic kidney disease (CKD), dialysis, and renal transplantation have many drawbacks [1]. We previously showed that rats with CKD treated with bone marrow-derived mesenchymal stem cells (BMSCs) injected into the renal parenchyma did stabilize the progression of disease [2]. Pluripotent stem cells have driven attention to approaches aiming to treat some human diseases, and their. Stem Cells International potential in regenerative nephrology comprises a spectrum from repairing the chronically damaged kidney, at its different stages of the disease, to the establishment of a new functional whole kidney [4]. Embryonic stem cells (ESCs) are pluripotent, have the potential to be self-renewing, and can differentiate into tissues derived from the three germ layers. It was demonstrated that induced pluripotent stem (iPS) cells are reprogrammed from fibroblasts by ectopically expressing factors known to be highly expressed in murine ESCs [6,7,8,9]. There is a concern that virally established cell lines might lead to the development of tumors [10]

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