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Updated: Jul 1, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Activated SOX9+ renal epithelial cells promote kidney repair through secreting factors
Hao Nie1, Zixian Zhao1, Dewei Zhou1
1East Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract:
A broad spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures, leading to renal function loss. Following injury, a spectrum of tissue-resident epithelial stem/progenitor cells are known to be activated and then differentiate into mature renal cells to replace the damaged renal epithelium. Here, however, we reported an alternative way that tissue-resident cells could be activated to secrete multiple factors to promote organ repair. At single-cell resolution, we showed that the resident SOX9+ renal epithelial cells (RECs) could expand in the acutely injured kidney of both mouse and human. Compared to other cells, the SOX9+ RECs overexpressed much more secretion related genes, whose functions were linked to kidney repair pathways. We also obtained long-term, feeder-free cultured SOX9+ RECs from human urine and analysed their secretory profile at both transcriptional and proteomic levels. Engraftment of cultured human SOX9+ RECs or injection of its conditional medium facilitated the regeneration of renal tubular and glomerular epithelium, probably through stimulating endogenous REC self-activation and mediating crosstalk with other renal cells. We also identified S100A9 as one of the key factors in the SOX9+ REC secretome. Altogether, the abilities to extensively propagate SOX9+ RECs in culture whilst concomitantly maintaining their intrinsic secretory capacity suggest their future application in cell-free therapies and regeneration medicine.
Insights
Resident SOX9+ renal epithelial cells (RECs) expand and secrete factors promoting kidney repair. Cultured human SOX9+ RECs and their secretome aid renal regeneration, suggesting cell-free therapy potential.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Kidney diseases often cause irreversible tubular destruction and renal function loss.
- Tissue-resident stem/progenitor cells typically activate and differentiate to replace damaged renal epithelium.
- An alternative mechanism involving secreted factors for organ repair is explored.
Purpose of the Study:
- To investigate the role of resident SOX9+ renal epithelial cells (RECs) in kidney repair.
- To analyze the secretory profile and regenerative potential of cultured SOX9+ RECs.
- To identify key factors involved in SOX9+ REC-mediated kidney regeneration.
Main Methods:
- Single-cell analysis of injured mouse and human kidneys.
- Isolation and long-term culture of human SOX9+ RECs from urine.
- Transcriptional and proteomic analysis of SOX9+ REC secretome.
- In vivo studies involving SOX9+ REC engraftment and conditional medium injection.
Main Results:
- SOX9+ RECs were found to expand in acutely injured kidneys (mouse and human).
- SOX9+ RECs overexpressed genes related to secretion and kidney repair pathways.
- Cultured human SOX9+ RECs and their secretome promoted renal tubular and glomerular regeneration.
- S100A9 was identified as a key secreted factor.
Conclusions:
- SOX9+ RECs represent an alternative pathway for kidney repair through secretion of regenerative factors.
- Cultured SOX9+ RECs maintain their secretory capacity, offering potential for cell-free therapies.
- These findings highlight the therapeutic potential of SOX9+ RECs in regenerative medicine for kidney diseases.
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