Reprogramming human adult renal cells for kidney regeneration
As dialysis and kidney transplantation are currently the only successful therapies for patients suffering from end stage renal disease, and these approaches are limited by patient morbidity and organ shortages, cell therapy with renal stem/progenitor cells may offer an alternative approach for treatment of renal diseases. The nephron, the kidney's functional unit, arises during development from a self renewing pool of multipotent nephron forming cells. This population becomes extinguished shortly after birth in the mouse and at the 34-week of human gestation, rendering the postnatal kidney unable to regenerate new nephrons in response to kidney injury. Reprogramming of adult kidney cells backwards into early multipotent nephron forming cells that can be grown in culture are a crucial to neo-nephrogenesis, kidney regeneration and kidney engineering. Preliminary data from our labs suggests that ectopic expression in adult kidney cells of pluripotent factors such as LIN28 and OCT4 and nephrogenic factors such as OSR1, SIX2, PAX2 might lead to reprogramming of these cells into early kidney progenitors, and thus, to a new source of nephron forming cells. Our data suggest that none of these factors alone leads to a multi-potent state. In this project we propose to further study the role of each of these genes in renal reprogramming, and then to define the ideal combination of pluripotent and nephrogenic factors required for reprogramming of adult kidney cells into expandable and functional “induced Nephron-Forming” (iNF) cells. Success in deriving iNF cells promises to have a revolutionary impact on the field of renal medicine.to have a revolutionary impact on the field of renal medicine.

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