In vitro differentiation of induced pluripotent stem cells (iPS) in renal progenitor cells and their effect on treatment of experimental chronic renal failure

Abstract

Chronic renal failure (CRF) is characterized by progressive and irreversible loss of kidney function and its treatment generates a significant public cost for maintenance of patients on dialysis. Therapy with stem cells is a promising strategy for the treatment of CRF. Studies have shown that the use of renal progenitor cells (RPCs) and induced pluripotent stem cells (iPS) during the acute kidney injury is effective, but the result of these cells in chronic renal failure and the simultaneous treatment compared between the cells is unknown. Taking into account that iPS are capable of generate tumor when transplanted due to the their pluripotent characteristic, alternative strategies for therapy are necessary. Thus, the project objectives are: 1) genetically modify fibroblasts from Wistar rats, aiming to transform somatic cells into iPS; 2) irradiating the iPS cells and induce differentiation of portion of the obtained iPS in multipotent RPCs, making their use potentially safer; 3) evaluate the effects of RPCs and irradiated iPS in the treatment of CRF. The project will be performed in partnership with the Núcleo de Terapia Celular e Molecular - NUCEL - IQ / USP coordinated by Prof. Dr. Mari Sogayar (collaboration letter attached) which will assist in reprogramming of fibroblasts into iPS through the use of lentiviral vectors containing transcription factors. Also they will assist in irradiating of the iPS and differentiation of iPS in RPCs by using a cocktail of nephrogenic factors in culture. Then, the obtained RPCs and irradiated iPS will be transplanted into experimental model of CRF in rats, and the efficacy of each therapies will be assessed. The reduction of tumor formation and the improvement of CRF are the expected results. (AU)