Dreaming of no more renal dialysis: how self-deriv.. (RESET)
Dreaming of no more renal dialysis: how self-derived tissue and cells can replace renal function
Start date: May 1, 2011,
End date: Apr 30, 2016
"For chronic kidney diseases there is little chance that the vast majority of the world¿s population will have access to renal replacement therapy with dialysis. There is yet no adequate alternative with curative intent than allo-transplantation. This approach is seriously impaired by eventually limited graft survival and by the scarce availability of donors. We propose an innovative strategy that would help to simultaneously overwhelm the reduced access to dialysis, the need for organs for transplantation, the avoidance of patient exposure to immunosuppressants. The overall focus is based on the idea of generating new kidneys by tissue engineering technologies starting from a whole-kidney scaffold with intact three-dimensional geometry and vasculature created by de-cellularization of a kidney harvested from the patient with progressive chronic kidney disease (CKD). Repopulation of the kidney scaffold could be achieved with patient-specific induced pluripotent stem (iPS) cells generated by reprogramming to a pluripotent status of somatic cells. After regeneration, the kidney will be transplanted in the same patient. Thereafter, the same procedures will be repeated with the contralateral native injured kidney, after in vivo assessment of the proper functional performance of the newly generated transplanted organ.This goal will be pursued through the three steps introductory to the development of the best strategy for translating the proposed frontier research to patients with CKD:1.Create an intact whole-kidney scaffold by de-cellularization of a rodent kidney and validate theprocedure with a human kidney.2. Attempt to reconstruct the organ by reseeding the rodent and human whole-kidney scaffoldswith iPS cells generated by reprogramming adult dermal fibroblasts to a pluripotent status.3. Deeply characterize the function of the new rodent and human kidneys by in vivo and in vitrotechniques."
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