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Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells
Published on: August 29, 2016
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Generation of a Humanized Mouse Liver Using Human Hepatic Stem Cells
Ran-Ran Zhang1, Yun-Wen Zheng2, Hideki Taniguchi1
1Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University.
Journal of Visualized Experiments : Jove
|September 30, 2016
Summary
A new Alb-TRECK/SCID mouse model enables humanized liver generation using immature human hepatic stem cells. This model advances preclinical research in drug metabolism and hepatic cell biology.
Area of Science:
- Hepatology and Regenerative Medicine
- Preclinical Drug Development Models
Background:
- Humanized liver models are crucial for studying hepatic cell biology and drug metabolism.
- Existing models using fumarylacetoacetate hydrolase (Fah) or uroplasminogen activator (uPA) mice have limitations, including restricted use with mature hepatocytes or breeding difficulties.
Purpose of the Study:
- To develop a novel, improved animal model for generating humanized livers.
- To overcome limitations of existing models for in vivo differentiation of immature human hepatocytes.
Main Methods:
- Utilized Alb-toxin receptor mediated cell knockout (TRECK)/SCID mice for liver repopulation.
- Transplanted immature human hepatic stem cells (HpSCs) into mice induced with lethal fulminant hepatic failure via diphtheria toxin (DT).
Main Results:
- Successful repopulation of Alb-TRECK/SCID mouse livers with functional human hepatocytes.
- Demonstrated in vivo differentiation and expansion of human hepatic stem cells in the engineered microenvironment.
Conclusions:
- The Alb-TRECK/SCID mouse model provides a robust platform for generating humanized livers from immature cells.
- This model is highly applicable for preclinical studies on drug metabolism, drug-drug interactions, and hepatic cell biology.
