[关键词]
[摘要]
类器官作为一种新型体外研究系统,可高度模拟体内组织、器官的功能结构和遗传特征等生物学特性。目前,肠道、视网膜、脑、肾、胰腺和肺等健康组织的类器官模型已逐渐建立。近年来,肝胆类器官也成为相关领域的研究热点。相较于传统的原代肝细胞、人源肝细胞系和动物模型,肝胆类器官能在维持一定遗传稳定性的前提下,在体外长期增殖并具备成熟的肝胆系统功能,具有开发为临床前药物肝脏效毒评价平台的潜力。就近年来肝胆类器官建立的来源途径、分化方法优化、分化效果评价,以及利用肝胆类器官平台对中药药效/毒效的评估展开论述,以期建立一种可准确、高效反映药物作用机制的模型,并用于大规模药物筛选、疾病机制研究及个体化精准医疗,为新药开发、药物评价及临床用药等提供新的策略方案。
[Key word]
[Abstract]
Organoids are in vitro cell models with specific organ functions and genetic characteristics, which are induced and differentiated from stem cells. Recently, the organoids obtained from healthy tissues such as the gut, retina, brain, kidney, pancreas and lung have gradually been established. In the meanwhile, hepatobiliary organoids have become a research hotspot in related fields. Compared with primary hepatocytes, human liver cell lines and animal models, hepatobiliary organoids are able to maintain genetic stability, achieve long-term proliferation and possess the characteristics of a mature hepatobiliary system in vitro, which gives them the potential to be developed as a model for liver efficacy/toxicity evaluation of pre-clinical drugs. In this review, we summarize the source of hepatobiliary organoids, the optimization of differentiation methods and the evaluation of differentiation effects, comprehensively introduce the pharmacological and toxic research of hepatobiliary organoids-based traditional Chinese medicine to establish an accurate and efficient model reflecting the mechanism of drug action. Further hepatobiliary organoids research will contribute to the investigation of the pathogenesis of diseases and the development of large-scale drug screening and individualized precision medicine, providing new strategies for novel drug development, drug evaluation and therapeutic medication with an alluring prospect in the clinical application.
[中图分类号]
R28
[基金项目]
北京市科技新星课题(Z191100001119088);北京市双一流课题(1000041510168)