A nonhuman primate model of liver fibrosis towards cell therapy for liver cirrhosis.
Biochem Biophys Res Commun
; 526(3): 661-669, 2020 06 04.
Article
in En
| MEDLINE
| ID: mdl-32248968
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatocytes
/
Induced Pluripotent Stem Cells
/
Liver Cirrhosis
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2020
Document type:
Article