Semin Cell Dev Biol. 2014 Aug 13. pii: S1084-9521(14)00238-9. doi: 10.1016/j.semcdb.2014.08.003. [Epub ahead of print]

Kidney stem cells in development, regeneration and cancer.

Dziedzic K¹, Pleniceanu O¹, Dekel B².

Abstract

End-stage renal failure is a major cause of death with currently only dialysis and transplantation available as therapeutic options, each with its own limitations and draw-backs. To allow regenerative medicine-based renal replacement therapies, much attention has been given to finding kidney-forming stem/progenitor cells in embryonic and adult kidney tissues. The generation of nephrons during development is generally thought to depend on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In-vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex-vivo preserve and expand the observed in vivo kidney - forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephronstem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells towards expandable renal progenitors.