Embryonic committed stem cells as a solution to kidney donor shortage

Abstract

The number of human kidney transplants has increased rapidly in recent years, but the need greatly exceeds organ availability. Induction of appropriate kidney differentiation and growth from stem or progenitor cell populations represents an attractive option to combat chronic kidney donor shortage. In an analogy to haematopoietic stem cells, which are much more efficient in giving rise to blood than to other cell types, if any at all, renal stem cells could afford an unlimited source for regenerating nephrons. While a single nephrogenic stem cell has not been characterised, indirect evidence suggests that a renal stem cell population is contained within the metanephric mesenchyme, which along with a branch of the Wolffian duct represents the direct precursor of the mature kidney. Human tissue fragments derived from these developing precursors can regenerate renal structures when grafted into mice. Moreover, recent data pinpoints a window of time in human and pig kidney development that may be optimal for transplantation into mature recipients. ‘Window’ transplants are defined by their remarkable ability to grow, differentiate and undergo vascularisation, achieving successful organogenesis of urine-producing miniature kidneys with no evidence of transdifferentiation into non-renal cell types, lack of tumourigenicity and reduced immunogenicity compared with adult counterparts. In contrast, ‘non-window’ transplants (earlier or later in gestation) can form teratomas or are more prone to immune rejection and are less suitable for organogenesis. Hopefully, the use of stage-specific early human and porcine kidney precursors to cultivate mature kidney cells in vivo, possibly in conjunction with other modalities of stem cell technology and tissue engineering, will prove valuable to sustain life in patients with failing kidneys.