Identification and prospective isolation of novel human renal stem/progenitor populations from normal and cancerous kidney tissue

The precursor of the adult mammalian kidney is called the metanephros and it appears at 5 weeks of human gestation, equivalent to embryonic day 11 in mice and day 12 in rats. At this stage, the organ consists of ureteric bud epithelium which becomes enveloped by renal mesenchyme/blastema: these tissues form collecting ducts and nephron tubules, respectively. In the developing human kidney, fresh stem cells are induced into the nephrogenic pathway to form nephrons until 34 weeks of gestation.

Others and we have shown that two pathologic situations strongly recapitulate this developmental program by activating specific transcription factors that mark the early renal progenitor population: (i) renal regeneration following episodes of acute injury, suggestive of the presence of adult kidney stem cells (ii) renal tumorigenesis in the form of a Wilms´tumor, a common pediatric kidney cancer, believed to arise from multipotent embryonic renal precursors of the renal mesenchyme/ blastema. Thus, the renal progenitor pool is likely to be at the heart of all of these processes.

Recent molecular advances have much contributed to our understanding of the cell lineages in the developing kidney. Nevertheless, in contrast with other organs, such as the hematopoietic system, in which the identification of surface markers enabled purification of these cells, the lack of such in the kidney has hampered progress in identifying and isolating stem cells. Microarray experiments, cell selection strategies, clonal analysis and various in vivo assays of human cells derived from normal and cancerous kidney tissue have now afforded insights into relevant shared stem cell markers and accordingly to human renal stem/progenitor populations.
This may enable the potential application of renal stem cells in kidney repair and the treatment of kidney cancers.