Adult Stem Cell-like Tubular Cells Reside in the Corticomedullary Junction of the Kidney

The existence of adult renal stem cells has long been suspected because the kidney is capable of regeneration in response to injury, such as acute tubular necrosis (ATN), but their location, or niche, has not been fully defined yet. The aim of this study was to identify the niche of adult renal stem cells responsible for the tubular regeneration. The location of label-retaining cells (LRCs) was studied in adult mouse kidneys after administration of a pulse of bromodeoxyuridine (BrdU) during embryonic period. To study regional participation in renal tubular regeneration, the expression of the proliferation marker Ki-67 was examined after induction of unilateral ATN in mouse kidneys. Regional colony-forming capacity was examined using cultured cells derived from normal mouse and human kidneys and their multipotency was examined in human kidneys. LRCs in adult mouse kidneys were mostly tubular epithelial cells and concentrated constantly in the outer stripe of the corticomedullary junction (CMJ). In the ATN model, Ki-67 positive cells were concentrated in the tubular epithelial cells of the outer stripe, not only in the ATN kidneys but also in the contralateral non-ATN kidneys. High colony-forming capacity was noted in the CMJ of mouse and human kidneys. Cultured cells derived from a single human CMJ cell revealed multipotency, differentiating not only into tubular cells but also into glomerular podocytes. These results demonstrate that the CMJ of the kidney contains label-retaining, renal-repairing, highly colony-forming multipotent stem cell-like tubular cells, suggesting the CMJ as the niche of adult renal stem cells.