基础医学与临床2025，Vol.45Issue(5)：589-598,10.DOI:10.16352/j.issn.1001-6325.2025.05.0589
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
Constructing a research model for liver regeneration by using hepatocyte-like organoid derived from human pluripotent stem cells
摘要
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.关键词
肝脏再生/肝细胞样类器官/CRISPR/Cas9/人多能干细胞Key words
liver regeneration/hepatocyte-like organoid/CRISPR/Cas9/human pluripotent stem cell分类
生物学引用本文复制引用
王晨曦,杨淑春,贾玉艳,黄粤..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[J].基础医学与临床,2025,45(5):589-598,10.基金项目
国家自然科学基金(32370898) （32370898）
