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Kidney stem/progenitor cells as a potent source for kidney-targeted cell therapy

Kidney failure is associated with high morbidity, mortality and costs. It is caused by the irreversible loss of nephrons, the functional units of the kidney. The nephrons are derived from a stem/progenitor cell population, which is exhausted at the 36th week of gestation when nephrogenesis ends. After birth, no new nephrons develop, which limits regeneration. We found a novel source of kidney stem/progenitor cells (nKSPCs) in the urine of neonates born prematurely, when the progenitors cells were still active. nKSPCs can differentiate into functional kidney cells and have immunomodulatory capacity. Upon perfusion in normothermic machine perfusion (NMP), nKSPCs could be traced in a human kidney, which showed reduced inflammation and reactivation of nephrogenesis genes, suggesting initiation of a regenerative process. We hypothesize that nKSPCs are the ideal source for kidney-targeted cell-therapy, providing immunomodulation and regeneration to kidney tissue. We will elucidate, in vitro, the immunomodulatory profile of nKSPCs (WP1), and their regenerative potential in human kidney (WP2). In WP3, we will use NMP to assess ex-vivo the potential of nKSPCs to improve quality and function of kidneys discarded for transplantation. In WP4, we will generate and validate clinical grade nKSPCs to be applied in human kidney cell therapy. Once successful, nKSPCs will represent a potent source of cells to treat kidney diseases and revolutionize kidney regenerative medicine.
Date:1 Oct 2021 →  Today
Keywords:cell therapy, Kidney stem cells, Kidney transplantation, Regenerative medicine
Disciplines:Transplantation immunology, Kidney transplantation, Cell therapy