A nonhuman primate model of liver fibrosis towards cell therapy for liver cirrhosis

Katsutaro Yasuda, Maki Kotaka, Takafumi Toyohara, Shin Ichi Sueta, Yuko Katakai, Naohide Ageyama, Shinji Uemoto, Kenji Osafune

Research output: Contribution to journalArticle

Abstract

Orthotopic liver transplantation (OLT) is the only curative treatment for refractory chronic liver failure in liver cirrhosis. However, the supply of donated livers does not meet the demand for OLT due to donor organ shortage. Cell therapy using hepatocyte-like cells derived from human induced pluripotent stem cells (hiPSC-HLCs) is expected to mitigate the severity of liver failure, postpone OLT and ameliorate the insufficient liver supply. For the successful clinical translation of hiPSC-based cell therapy against liver cirrhosis, realistic animal models are required. In this study, we created a nonhuman primate (NHP) liver fibrosis model by repeated administrations of thioacetamide (TAA) and evaluated the short-term engraftment of hiPSC-HLCs in the fibrotic liver. The NHP liver fibrosis model reproduced well the pathophysiology of human liver cirrhosis including portal hypertension. Under immunosuppressive treatment, we transplanted ALBUMIN-GFP reporter hiPSC-HLC aggregates into the fibrotic livers of the NHP model via the portal vein. Fourteen days after the transplantation, GFP-expressing hiPSC-HLC clusters were detected in the portal areas of the fibrotic livers. These results will facilitate preclinical studies using the NHP liver fibrosis model and help establish iPSC-based cell therapies against liver cirrhosis.

Original languageEnglish
Pages (from-to)661-669
Number of pages9
JournalBiochemical and biophysical research communications
Volume526
Issue number3
DOIs
Publication statusPublished - 2020 Jun 4
Externally publishedYes

Keywords

  • Cell therapy
  • Liver cirrhosis
  • NHP model
  • iPSC

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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