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Updated: Apr 6, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in
Takafumi Toyohara1, Shin-Ichi Mae1, Shin-Ichi Sueta1
1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Clinical Research Center, Chiba University of Medicine, Chiba, Japan; Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Unlabelled:
Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting from various etiologies, with a mortality rate exceeding 60% among intensive care patients. Because conventional treatments have failed to alleviate this condition, the development of regenerative therapies using human induced pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for AKI. We describe our methodology for generating renal progenitors from hiPSCs that show potential in ameliorating AKI. We established a multistep differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors capable of reconstituting three-dimensional proximal renal tubule-like structures in vitro and in vivo. Moreover, we found that renal subcapsular transplantation of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by ischemia/reperfusion injury, significantly suppressing the elevation of blood urea nitrogen and serum creatinine levels and attenuating histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of cell therapy with renal lineage cells generated from hiPSCs have been published. Our results suggest that regenerative medicine strategies for kidney diseases could be developed using hiPSC-derived renal cells.
Significance:
This report is the first to demonstrate that the transplantation of renal progenitor cells differentiated from human induced pluripotent stem (iPS) cells has therapeutic effectiveness in mouse models of acute kidney injury induced by ischemia/reperfusion injury. In addition, this report clearly demonstrates that the therapeutic benefits come from trophic effects by the renal progenitor cells, and it identifies the renoprotective factors secreted by the progenitors. The results of this study indicate the feasibility of developing regenerative medicine strategy using iPS cells against renal diseases.
Insights
Human induced pluripotent stem cells (hiPSCs) can be differentiated into renal progenitors to treat acute kidney injury (AKI). Transplanted hiPSC-derived renal cells improved kidney function and reduced damage in mice with AKI.
Area of Science:
- Nephrology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Acute kidney injury (AKI) is a critical condition with high mortality and limited treatment options.
- Conventional therapies are insufficient for AKI, necessitating novel approaches like regenerative medicine.
- Human induced pluripotent stem cells (hiPSCs) offer a promising source for developing cell-based therapies for AKI.
Purpose of the Study:
- To develop a method for generating renal progenitor cells from hiPSCs.
- To evaluate the therapeutic potential of hiPSC-derived renal progenitors in ameliorating AKI.
- To investigate the mechanisms underlying the therapeutic effects of these cells.
Main Methods:
- Established a multistep differentiation protocol to generate OSR1+SIX2+ renal progenitors from hiPSCs.
- Assessed the ability of these progenitors to form three-dimensional renal tubule-like structures in vitro and in vivo.
- Transplanted hiPSC-derived renal progenitors into mice with ischemia/reperfusion-induced AKI.
Main Results:
- hiPSC-derived renal progenitors successfully formed renal tubule-like structures.
- Transplantation of these progenitors significantly improved kidney function in AKI mice, indicated by reduced blood urea nitrogen and serum creatinine levels.
- Histopathological analysis revealed attenuated tubular necrosis, dilatation with casts, and interstitial fibrosis in treated mice.
Conclusions:
- This study is the first to demonstrate the therapeutic efficacy of transplanted hiPSC-derived renal progenitor cells in a mouse model of AKI.
- The therapeutic benefits are attributed to trophic effects and the secretion of renoprotective factors by the progenitor cells.
- These findings support the feasibility of developing regenerative medicine strategies using hiPSC-derived cells for kidney diseases.
