Human iPSC Used To Treat Kidney Injury In Mice

A public-private partnership between CiRA and Astellas has yielded the finding that iPSC could be used to treat acute kidney injury.

AsianScientist (Jul. 29, 2015) – Together with researchers from Astellas Pharma Inc., Professor Kenji Osafune’s group at Center for iPS Cell Research and Application (CiRA), Kyoto University, have used induced pluripotent stem cells (iPSC) to treat acute kidney injury in mice. Their results have been published in Stem Cells Translational Medicine.

Acute kidney injury is defined as a rapid loss of renal function, with a mortality rate exceeding 60 percent among intensive care patients. Previous reports suggest that iPSC are a promising alternative to conventional treatment, with one group reporting that iPSC-derived renal progenitors ameliorate renal injury in mouse models.

The transcription factors Osr1 and Six2 are known to interact synergistically to maintain nephron progenitor status during kidney organogenesis, and the combination of Osr1 and Six2 can be used as a specific marker set to define nephron progenitors.

In the present study, The researchers established a novel protocol to efficiently differentiate human iPSCs into OSR1+SIX2+ renal progenitors, and demonstrated the progenitors were able to form proximal renal tubule-like structures in vitro and in vivo.

Moreover, in an ischemia/reperfusion-induced AKI mouse model, transplanting these cells into the mouse kidney significantly suppressed the elevation of blood urea nitrogen and serum creatinine levels and attenuated histopathological changes, such as tubular necrosis, tubule dilatation with casts, and interstitial fibrosis. The fact that the transplanted renal progenitor cells did not engraft indicates that trophic factors secreted from the cells were responsible for the protective effects of the treatment.

These findings therefore suggest that cell therapy using hiPSC-derived renal progenitors might become one of therapeutic options for AKI patients by ameliorating renal tissue damage and possibly preventing transition to chronic tissue damage. Based on the findings, Astellas and CiRA will explore the possibility to develop new cell-based therapies for not only AKI but also chronic kidney disease.

The article can be found at: Toyohara et al. (2015) Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors Ameliorates Acute Kidney Injury in Mice.

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Source: Astellas; Photo: Shutterstock.
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