• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

基于干细胞的肝细胞样细胞模型在肝毒性测试中的进展。

Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.

机构信息

Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510000, China.

Department of Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Stem Cell Res Ther. 2021 Jan 25;12(1):84. doi: 10.1186/s13287-021-02152-9.

DOI:10.1186/s13287-021-02152-9
PMID:33494782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7836452/
Abstract

Drug-induced liver injury (DILI) is one of the leading causes of clinical trial failures and high drug attrition rates. Currently, the commonly used hepatocyte models include primary human hepatocytes (PHHs), animal models, and hepatic cell lines. However, these models have disadvantages that include species-specific differences or inconvenient cell extraction methods. Therefore, a novel, inexpensive, efficient, and accurate model that can be applied to drug screening is urgently needed. Owing to their self-renewable ability, source abundance, and multipotent competence, stem cells are stable sources of drug hepatotoxicity screening models. Because 3D culture can mimic the in vivo microenvironment more accurately than can 2D culture, the former is commonly used for hepatocyte culture and drug screening. In this review, we introduce the different sources of stem cells used to generate hepatocyte-like cells and the models for hepatotoxicity testing that use stem cell-derived hepatocyte-like cells.

摘要

药物性肝损伤(DILI)是临床试验失败和高药物淘汰率的主要原因之一。目前,常用的肝细胞模型包括原代人肝细胞(PHH)、动物模型和肝细胞系。然而,这些模型存在物种特异性差异或不方便的细胞提取方法等缺点。因此,迫切需要一种新型的、廉价的、高效的、准确的可应用于药物筛选的模型。由于其自我更新能力、来源丰富和多能性,干细胞是药物肝毒性筛选模型的稳定来源。由于 3D 培养比 2D 培养更能准确模拟体内微环境,前者常用于肝细胞培养和药物筛选。在这篇综述中,我们介绍了用于生成肝样细胞的不同来源的干细胞,以及使用干细胞衍生的肝样细胞进行肝毒性测试的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b6/7836452/ff1c919ee260/13287_2021_2152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b6/7836452/ff1c919ee260/13287_2021_2152_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2b6/7836452/ff1c919ee260/13287_2021_2152_Fig1_HTML.jpg

相似文献

1
Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.基于干细胞的肝细胞样细胞模型在肝毒性测试中的进展。
Stem Cell Res Ther. 2021 Jan 25;12(1):84. doi: 10.1186/s13287-021-02152-9.
2
Technological advancements for the development of stem cell-based models for hepatotoxicity testing.用于开发基于干细胞的肝毒性测试模型的技术进展。
Arch Toxicol. 2019 Jul;93(7):1789-1805. doi: 10.1007/s00204-019-02465-y. Epub 2019 Apr 29.
3
Human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening.源自多能干细胞的人肝细胞:一种用于药物肝毒性筛选的有前景的细胞模型。
Arch Toxicol. 2016 Sep;90(9):2049-2061. doi: 10.1007/s00204-016-1756-1. Epub 2016 Jun 20.
4
Generation of hepatic spheroids using human hepatocyte-derived liver progenitor-like cells for hepatotoxicity screening.使用人源性肝祖细胞样细胞生成肝球体用于肝毒性筛选。
Theranostics. 2019 Sep 18;9(22):6690-6705. doi: 10.7150/thno.34520. eCollection 2019.
5
Toxicological applications of human induced pluripotent stem cell-derived hepatocyte-like cells: an updated review.人诱导多能干细胞衍生的肝细胞样细胞在毒理学中的应用:最新综述。
J Toxicol Sci. 2023;48(8):441-456. doi: 10.2131/jts.48.441.
6
Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells.利用源自人类胚胎干细胞的类肝细胞预测药物诱导的免疫介导性肝毒性。
Toxicology. 2017 Jul 15;387:1-9. doi: 10.1016/j.tox.2017.06.005. Epub 2017 Jun 20.
7
Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury.用于评估药物性肝损伤的干细胞衍生肝样细胞
Differentiation. 2019 Mar-Apr;106:15-22. doi: 10.1016/j.diff.2019.02.004. Epub 2019 Feb 19.
8
Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research.利用三维纳米纤维(HYDROX)高效分化原代人肝细胞来源的类器官及其在肝毒性研究中的可能应用。
Sci Rep. 2024 May 13;14(1):10846. doi: 10.1038/s41598-024-61544-y.
9
Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.用于药物毒性筛选的人多能干细胞来源的肝样细胞的生成。
Drug Metab Pharmacokinet. 2017 Feb;32(1):12-20. doi: 10.1016/j.dmpk.2016.10.408. Epub 2016 Oct 26.
10
Co-Culture of Human Primary Hepatocytes and Nonparenchymal Liver Cells in the Emulate® Liver-Chip for the Study of Drug-Induced Liver Injury.在 Emulate® Liver-Chip 中共培养人原代肝细胞和非实质肝细胞以研究药物性肝损伤。
Curr Protoc. 2022 Jul;2(7):e478. doi: 10.1002/cpz1.478.

引用本文的文献

1
Advancing hepatotoxicity assessment: current advances and future directions.推进肝毒性评估:当前进展与未来方向
Toxicol Res. 2025 Apr 24;41(4):303-323. doi: 10.1007/s43188-025-00289-w. eCollection 2025 Jul.
2
Functional Liver Cell-Based Platforms in Biomedical Research.生物医学研究中基于功能性肝细胞的平台
Pharmacol Res Perspect. 2025 Jun;13(3):e70128. doi: 10.1002/prp2.70128.
3
Single-cell transcriptomics reveals liver developmental trajectory during lineage reprogramming of human induced hepatocyte-like cells.单细胞转录组学揭示了人类诱导肝细胞样细胞谱系重编程过程中的肝脏发育轨迹。

本文引用的文献

1
Synthetic alternatives to Matrigel.基质胶的合成替代品。
Nat Rev Mater. 2020 Jul;5(7):539-551. doi: 10.1038/s41578-020-0199-8. Epub 2020 May 27.
2
Microfluidic organ-on-a-chip models of human liver tissue.人体肝脏组织的微流控芯片器官模型。
Acta Biomater. 2020 Oct 15;116:67-83. doi: 10.1016/j.actbio.2020.08.041. Epub 2020 Sep 2.
3
Repeated dose multi-drug testing using a microfluidic chip-based coculture of human liver and kidney proximal tubules equivalents.采用基于微流控芯片的人肝和肾近端小管等效物共培养物进行重复剂量多药物测试。
Cell Mol Life Sci. 2025 Apr 6;82(1):139. doi: 10.1007/s00018-025-05677-x.
4
Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.从化学诱导的肝祖细胞生成具有功能性胆管的人肝胆类器官。
Stem Cell Res Ther. 2024 Aug 26;15(1):269. doi: 10.1186/s13287-024-03877-z.
5
Evaluation of different media compositions promoting hepatocyte differentiation in the canine liver organoid model.犬肝类器官模型中促进肝细胞分化的不同培养基成分评估
Heliyon. 2024 Mar 25;10(7):e28420. doi: 10.1016/j.heliyon.2024.e28420. eCollection 2024 Apr 15.
6
Schisandrin B promotes hepatic differentiation from human umbilical cord mesenchymal stem cells.五味子乙素促进人脐带间充质干细胞向肝细胞分化。
iScience. 2024 Jan 15;27(2):108912. doi: 10.1016/j.isci.2024.108912. eCollection 2024 Feb 16.
7
Platform-agnostic CellNet enables cross-study analysis of cell fate engineering protocols.无平台限制的 CellNet 可实现细胞命运工程方案的跨研究分析。
Stem Cell Reports. 2023 Aug 8;18(8):1721-1742. doi: 10.1016/j.stemcr.2023.06.008. Epub 2023 Jul 20.
8
Distinct hepatocyte identities in liver homeostasis and regeneration.肝脏稳态与再生过程中不同的肝细胞特性
JHEP Rep. 2023 Apr 24;5(8):100779. doi: 10.1016/j.jhepr.2023.100779. eCollection 2023 Aug.
9
Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.regorafenib 通过 ERK/MDM2/p53 轴抑制 EphA2 磷酸化并导致肝损伤。
Nat Commun. 2023 May 13;14(1):2756. doi: 10.1038/s41467-023-38430-8.
10
Three-Dimensional Cell Co-Culture Liver Models and Their Applications in Pharmaceutical Research.三维细胞共培养肝模型及其在药物研究中的应用。
Int J Mol Sci. 2023 Mar 26;24(7):6248. doi: 10.3390/ijms24076248.
Sci Rep. 2020 Jun 1;10(1):8879. doi: 10.1038/s41598-020-65817-0.
4
Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies.用于物质暴露研究的支气管肺培养和肝球体的人多器官芯片共培养
Sci Rep. 2020 May 12;10(1):7865. doi: 10.1038/s41598-020-64219-6.
5
Human-on-Leaf-Chip: A Biomimetic Vascular System Integrated with Chamber-Specific Organs.人在叶芯片上:与腔特异性器官集成的仿生血管系统。
Small. 2020 Jun;16(22):e2000546. doi: 10.1002/smll.202000546. Epub 2020 Apr 24.
6
Oxygen Plasma Substrate and Specific Nanopattern Promote Early Differentiation of HepaRG Progenitors.氧等离子体底物和特定纳米图案促进HepaRG祖细胞的早期分化。
Tissue Eng Part A. 2020 Oct;26(19-20):1064-1076. doi: 10.1089/ten.TEA.2019.0241.
7
Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines.氨基酸水平决定肝细胞和肝癌细胞株的代谢和 CYP450 功能。
Nat Commun. 2020 Mar 13;11(1):1393. doi: 10.1038/s41467-020-15058-6.
8
Drug compound screening in single and integrated multi-organoid body-on-a-chip systems.药物化合物在单个和集成多器官芯片系统中的筛选。
Biofabrication. 2020 Feb 26;12(2):025017. doi: 10.1088/1758-5090/ab6d36.
9
Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids.纤维素纳米原纤维水凝胶促进人肝脏类器官的肝分化。
Adv Healthc Mater. 2020 Mar;9(6):e1901658. doi: 10.1002/adhm.201901658. Epub 2020 Feb 23.
10
Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?动物研究在预测临床试验中毒性方面的局限性:是时候重新思考我们当前的方法了吗?
JACC Basic Transl Sci. 2019 Nov 25;4(7):845-854. doi: 10.1016/j.jacbts.2019.10.008. eCollection 2019 Nov.