The renal papilla is a niche for adult kidney stem cells
Juan A. Oliver, Omar Maarouf, Faisal H. Cheema, Timothy P. Martens, Qais Al-Awqati
Juan A. Oliver, Omar Maarouf, Faisal H. Cheema, Timothy P. Martens, Qais Al-Awqati
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Article Nephrology

The renal papilla is a niche for adult kidney stem cells

Abstract

Many adult organs contain stem cells, which are pluripotent and are involved in organ maintenance and repair after injury. In situ, these cells often have a low cycling rate and locate in specialized regions (niches). To detect such cells in the kidney, we administered a pulse of the nucleotide bromodeoxyuridine (BrdU) to rat and mouse pups and, after a long (more than 2-month) chase, examined whether the kidney contained a population of low-cycling cells. We found that in the adult kidney, BrdU-retaining cells were very sparse except in the renal papilla, where they were numerous. During the repair phase of transient renal ischemia, these cells entered the cell cycle and the BrdU signal quickly disappeared from the papilla, despite the absence of apoptosis in this part of the kidney. In vitro isolation of renal papillary cells showed them to have a plastic phenotype that could be modulated by oxygen tension and that when injected into the renal cortex, they incorporated into the renal parenchyma. In addition, like other stem cells, papillary cells spontaneously formed spheres. Single-cell clones of these cells coexpressed mesenchymal and epithelial proteins and gave rise to myofibroblasts, cells expressing neuronal markers, and cells of uncharacterized phenotype. These data indicate that the renal papilla is a niche for adult kidney stem cells.

Authors

Juan A. Oliver, Omar Maarouf, Faisal H. Cheema, Timothy P. Martens, Qais Al-Awqati

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Effect of transient renal ischemia on papillary BrdU-retaining cells. Th...
Effect of transient renal ischemia on papillary BrdU-retaining cells. The presence of BrdU-retaining cells was examined in papillae of control kidneys and of kidneys subjected to transient ischemia. (A) In 100-μm papillary sections 3 weeks after ischemia, compared with control, there was a marked decrease in BrdU-retaining cells in the papilla of the ischemic kidney. (B) Sections 5 μm in thickness showed that while the papillary tip of the control kidney had numerous BrdU-retaining cells, that of the ischemic kidney had very few. (C) For quantification of the effect of renal ischemia on the number of BrdU-retaining cells, 6 rats 5 months of age were subjected to transient ischemia of the left kidney; 3 weeks later their kidneys were harvested and cells from different parts of both kidneys were stained for BrdU and analyzed by flow cytometry. In all graphs, the y axis shows the number of cells, while the x axis (FL2-H) shows the fluorescent intensity. MI is the area of positive cells. In the papillae of the nonischemic kidneys, the number of BrdU-retaining cells averaged 36% of the total cells, while in the papillae of the kidneys subjected to transient ischemia, this number was only 4%, as shown to the left of each histogram. Compared with the control kidney, the ischemic kidney also had a slight decrease in the number of BrdU-positive cells in the medulla and cortex, suggesting that the papillary BrdU-retaining cells had not simply migrated to other parts of the kidney. Scale bars: 50 μm.