Constructing a research model for liver regeneration by using hepatocyte-like organoid derived from human pluripotent stem cells
10.16352/j.issn.1001-6325.2025.05.0589
- VernacularTitle:利用人多能干细胞衍生的肝细胞样类器官构建肝脏再生的研究模型
- Author:
Chenxi WANG
1
;
Shuchun YANG
;
Yuyan JIA
;
Yue HUANG
Author Information
1. 中国医学科学院基础医学研究所 北京协和医学院基础学院医学遗传学系 重大疾病共性机制研究全国重点实验室,北京 100005
- Keywords:
liver regeneration;
hepatocyte-like organoid;
CRISPR/Cas9;
human pluripotent stem cell
- From:
Basic & Clinical Medicine
2025;45(5):589-598
- CountryChina
- Language:Chinese
-
Abstract:
Objective To construct an in vitro research model for studying human liver regeneration based on human pluripotent stem cells(hPSCs)-derived hepatocyte-like organoid(HLO).Methods The hPSCs-derived HLO was obtained by inducing differentiation and the regeneration model after liver injury was constructed by adding acetaminophen(APAP)at fixed time points in HLO culture conditions to simulate acute liver injury.Subse-quently,HLO with catenin/cadherin-associated protein beta 1(CTNNB1)knockout,a key gene regulating liver re-generation,was constructed using CRISPR/Cas9 gene editing technology,and regeneration experiments with APAP injury were performed.HLO as a model for liver regeneration studies was further evaluated by morphological observation,RT-qPCR,Western blot and pathological analysis.Results Morphology evidence as well as expres-sion of marker genes showed that hPSCs-derived HLO was able to initiate a post-injury regeneration response after APAP treatment.CTNNB1-deficient HLO showed delayed recovery in dimension and down-regulated or delayed ex-pression of related genes during post-injury regeneration as compared to control HLO.Conclusions A HLO-based hPSCs-derived human liver regeneration model is successfully constructed,which can be used for gene function studies during liver regeneration.
