肝脏类器官在肝脏疾病模型与移植治疗中的应用潜力  

Potential application of liver organoids in liver disease models and transplantation therapy

作　　者：袁维勃 刘婵 余丽梅 Yuan Weibo;Liu Chan;Yu Limei(Guizhou Key Laboratory of Cell Engineering,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China;Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine Co-Built by Province and Ministry of Education,Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Guizhou Stem Cell Clinical Application and New Drug Research and Development Engineering Research Center,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China;Guizhou Biotherapy Talent Base,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China;Zunyi Stem Cell and Regenerative Medicine Engineering Research Center,Affiliated Hospital of Zunyi Medical University,Zunyi 563003,Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院,贵州省细胞工程重点实验室,贵州省遵义市563003 [2]遵义医科大学教育部省部共建组织损伤修复与再生医学协同创新中心,贵州省遵义市563000 [3]遵义医科大学附属医院贵州省干细胞临床应用与新药研发工程研究中心,贵州省遵义市563003 [4]遵义医科大学附属医院贵州省生物治疗人才基地,贵州省遵义市563003 [5]遵义医科大学附属医院,遵义市干细胞与再生医学工程研究中心,贵州省遵义市563003

出　　处：《中国组织工程研究》2025年第8期1684-1692,共9页Chinese Journal of Tissue Engineering Research

基　　金：2023年国家自然科学基金地区科学基金项目(82360047),项目负责人:余丽梅。

摘　　要：背景:肝脏类器官对阐明肝脏疾病的确切病理机制及对肝脏疾病的治疗具有重要的意义。目的:总结目前国内外该领域的基础研究,回顾以往肝脏类器官的构建、疾病建模和移植治疗的重要研究进展,探讨肝脏类器官联合组织工程技术的应用前景。方法:检索PubMed数据库及中国知网数据库收录的相关文献,英文检索词为“liver,organoids,liver diseases”,中文检索词为“肝,类器官,肝脏疾病”,主要检索时限为2018年4月至2024年4月,通过人工阅读排除重复文献等,最终纳入94篇文献进行归纳分析。结果与结论:①肝脏类器官构建的种子细胞主要集中于成体细胞和多能干细胞,通过辅助各种细胞因子参与信号引导作用和细胞外基质提供3D微环境,促进类器官的产生,但是整体成熟度不高,有望通过结合组织工程技术改善这一问题;②体外疾病建模方面主要在简单疾病和单基因遗传病领域研究较多,类器官高度保留患者遗传特性,有望通过结合CRISPR-Cas9基因矫正和其他新兴技术模拟更复杂的肝脏疾病并阐明更深层次的病理机制;③体内移植治疗方面,肝脏类器官能够安全有效的植入,表现出惊人的肝功能替代潜力及组织再生能力,并且还可能通过与其他组织工程材料结合达到治疗目的。BACKGROUND:Liver organoids are of great significance to elucidate the exact pathological mechanism of liver diseases and the treatment of liver diseases.OBJECTIVE:To summarize the basic research in this field at home and abroad,review the important research progress in the construction of liver organoids,disease modeling and transplantation therapy,and discuss the application prospect of combined tissue engineering technology of liver organoids.METHODS:The relevant articles included in PubMed and CNKI databases were searched.The English and Chinese search terms were“liver,organoids,liver diseases.”The main search time was from April 2018 to April 2024.Duplicate literature was excluded by manual reading.Finally,94 articles were included for review and analysis.RESULTS AND CONCLUSION:The seed cells constructed by liver organoids are mainly concentrated in adult cells and pluripotent stem cells,which promote the generation of organoids by assisting various cytokines to participate in signal guidance and providing 3D microenvironment by extracellular matrix.However,the overall maturity is not high,which is expected to improve this problem by combining tissue engineering technology.In vitro disease modeling is mainly studied in the field of simple diseases and single-gene genetic diseases.Organoids highly retain patient genetic characteristics,and it is expected to simulate more complex liver diseases and clarify deeper pathological mechanisms by combining CRISPR-Cas9 gene correction and other emerging technologies.In vivo transplantation treatment,liver organoids can be safely and effectively implanted,showing amazing liver function replacement potential,tissue regeneration ability,and may also be combined with other tissue engineering materials to achieve therapeutic purposes.

关 键 词：肝脏类器官 干细胞 种子细胞 肝脏疾病 疾病建模 体内移植 综述 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R617