Cell therapy using human induced pluripotent stem cell-derived renal progenitors ameliorates acute kidney injury in mice

Takafumi Toyohara, Shin Ichi Mae, Shin Ichi Sueta, Tatsuyuki Inoue, Yukiko Yamagishi, Tatsuya Kawamoto, Tomoko Kasahara, Azusa Hoshina, Taro Toyoda, Hiromi Tanaka, Toshikazu Araoka, Aiko Sato-Otsubo, Kazutoshi Takahashi, Yasunori Sato, Noboru Yamaji, Seishi Ogawa, Shinya Yamanaka, Kenji Osafune

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

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.Weestablished 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.

Original languageEnglish
Pages (from-to)980-992
Number of pages13
JournalStem Cells Translational Medicine
Volume4
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1
Externally publishedYes

Keywords

  • Acute kidney injury
  • Cell- and tissue-based therapy
  • Induced pluripotent stem cells
  • Kidney
  • Nephrons
  • Renal progenitors
  • SIX2 protein

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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