多能干细胞向肝细胞的转化之路，迄至今日。
Pluripotent stem cells to hepatocytes, the journey so far.
作者信息
Palakkan Anwar A, Nanda Jyoti, Ross James A
机构信息
Tissue Injury and Repair Group, Clinical Sciences, Edinburgh Medical School, University of Edinburgh, EH16 4SB Edinburgh, UK.
出版信息
Biomed Rep. 2017 Apr;6(4):367-373. doi: 10.3892/br.2017.867. Epub 2017 Mar 1.
Abstract
Over the past several years, there has been substantial progress in the field of regenerative medicine, which has enabled new possibilities for research and clinical application. For example, there are ongoing efforts directed at generating functional hepatocytes from adult-derived pluripotent cells for toxicity screening, generating disease models or, in the longer term, for the treatment of liver failure. In the present review, the authors summarise recent developments in regenerative medicine and pluripotent stem cells, the methods and tissues used for reprogramming and the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells. In addition, the hepatic disease models developed using iPSC technologies are discussed, as well as the potential for gene editing.
摘要
在过去几年中，再生医学领域取得了重大进展，为研究和临床应用带来了新的可能性。例如，目前正在努力从成人多能干细胞中生成功能性肝细胞，用于毒性筛查、建立疾病模型，或者从长远来看用于治疗肝衰竭。在本综述中，作者总结了再生医学和多能干细胞的最新进展、用于重编程的方法和组织，以及诱导多能干细胞（iPSC）向肝细胞样细胞的分化。此外，还讨论了使用iPSC技术建立的肝脏疾病模型以及基因编辑的潜力。
相似文献
1
Pluripotent stem cells to hepatocytes, the journey so far.多能干细胞向肝细胞的转化之路，迄至今日。
Biomed Rep. 2017 Apr;6(4):367-373. doi: 10.3892/br.2017.867. Epub 2017 Mar 1.
2
Induced pluripotent stem cells as a source of hepatocytes.诱导多能干细胞作为肝细胞的来源。
Curr Pathobiol Rep. 2014 Mar;2(1):11-20. doi: 10.1007/s40139-013-0039-2.
3
Donor-Dependent and Other Nondefined Factors Have Greater Influence on the Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell Derived Hepatocyte-Like Cells.供体依赖性和其他未定义因素对诱导多能干细胞衍生的类肝细胞中的肝表型的影响大于起始细胞类型。
Stem Cells Transl Med. 2017 May;6(5):1321-1331. doi: 10.1002/sctm.16-0029.
4
Synergistic effects of carboxymethyl-hexanoyl chitosan, cationic polyurethane-short branch PEI in miR122 gene delivery: accelerated differentiation of iPSCs into mature hepatocyte-like cells and improved stem cell therapy in a hepatic failure model.羧甲基己酰壳聚糖、阳离子聚氨酯-短支链聚乙烯亚胺在miR122基因递送中的协同作用：加速诱导多能干细胞分化为成熟的肝细胞样细胞并改善肝衰竭模型中的干细胞治疗。
Acta Biomater. 2015 Feb;13:228-44. doi: 10.1016/j.actbio.2014.11.018. Epub 2014 Nov 21.
5
Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments.细胞外基质中诱导多能干细胞来源肝细胞的功能成熟——生物人工肝微环境的比较分析
Stem Cells Transl Med. 2016 Sep;5(9):1257-67. doi: 10.5966/sctm.2015-0235. Epub 2016 Jul 15.
6
Generation of high quality of hepatocyte-like cells from induced pluripotent stem cells with Parp1 but lacking c-Myc.从诱导多能干细胞中生成具有 PARP1 但缺乏 c-Myc 的高质量肝细胞样细胞。
J Chin Med Assoc. 2018 Oct;81(10):871-877. doi: 10.1016/j.jcma.2018.06.002. Epub 2018 Jul 13.
7
Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity.人多能干细胞及其衍生细胞模型在药物毒性评估中的应用。
Expert Opin Drug Metab Toxicol. 2019 Jan;15(1):61-75. doi: 10.1080/17425255.2019.1558207. Epub 2018 Dec 17.
8
Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells.利用源自尿液细胞的患者特异性诱导多能干细胞对甲型血友病进行建模。
Life Sci. 2014 Jul 11;108(1):22-9. doi: 10.1016/j.lfs.2014.05.004. Epub 2014 May 13.
9
Potential applications of induced pluripotent stem cells (iPSCs) in hepatology research.诱导多能干细胞（iPSC）在肝脏病学研究中的潜在应用。
Curr Stem Cell Res Ther. 2015;10(3):208-15. doi: 10.2174/1574888x10666150120105946.
10
Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells.在没有 c-Myc 的情况下重编程诱导多能干细胞分化为肝细胞样细胞。
Biomaterials. 2011 Sep;32(26):5994-6005. doi: 10.1016/j.biomaterials.2011.05.009. Epub 2011 Jun 11.
引用本文的文献
1
A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.体外细胞模型在药物相互作用预测和安全性评估新前沿的综述
Pharmaceutics. 2025 Jun 6;17(6):747. doi: 10.3390/pharmaceutics17060747.
2
Human-Induced Pluripotent Stem Cell-Derived Definitive Endoderm Bulk Up and Hepatic Differentiation.人诱导多能干细胞来源的确定内胚层扩增与肝脏分化。
Methods Mol Biol. 2025;2924:31-43. doi: 10.1007/978-1-0716-4530-7_3.
3
Liver organoids: updates on generation strategies and biomedical applications.肝脏类器官：生成策略与生物医学应用的最新进展
Stem Cell Res Ther. 2024 Aug 7;15(1):244. doi: 10.1186/s13287-024-03865-3.
4
Pluripotent Stem Cell-Derived Hepatocyte-like Cells: Induction Methods and Applications.多能干细胞诱导的肝细胞样细胞：诱导方法与应用。
Int J Mol Sci. 2023 Jul 18;24(14):11592. doi: 10.3390/ijms241411592.
5
Liver Organoid Potential Application for Hepatitis E Virus Infection.类肝器官在戊型肝炎病毒感染中的潜在应用。
Adv Exp Med Biol. 2023;1417:133-139. doi: 10.1007/978-981-99-1304-6_9.
6
Therapeutic effect of autologous bone marrow cells injected into the liver under the guidance of B‑ultrasound in the treatment of HBV‑related decompensated liver cirrhosis.B超引导下自体骨髓细胞注入肝脏治疗HBV相关失代偿期肝硬化的疗效
Exp Ther Med. 2022 Aug 22;24(4):633. doi: 10.3892/etm.2022.11570. eCollection 2022 Oct.
7
Generation of functional hepatocytes by forward programming with nuclear receptors.核受体正向重编程生成功能性肝细胞。
Elife. 2022 Aug 12;11:e71591. doi: 10.7554/eLife.71591.
8
Transcriptional and Epigenetic Consequences of DMSO Treatment on HepaRG Cells.DMSO 处理对 HepaRG 细胞的转录和表观遗传后果。
Cells. 2022 Jul 26;11(15):2298. doi: 10.3390/cells11152298.
9
Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells.仅从胚胎干细胞产生围绕单个输尿管芽树排列并包含内源性血管的肾类器官。
Sci Rep. 2022 Jul 22;12(1):12573. doi: 10.1038/s41598-022-16768-1.
10
Organoids to model liver disease.用于模拟肝脏疾病的类器官。
JHEP Rep. 2020 Oct 22;3(1):100198. doi: 10.1016/j.jhepr.2020.100198. eCollection 2021 Feb.
本文引用的文献
1
Comparison of the transcriptomic profile of hepatic human induced pluripotent stem like cells cultured in plates and in a 3D microscale dynamic environment.平板培养与三维微尺度动态环境下培养的人诱导多能干细胞样肝细胞转录组图谱比较
Genomics. 2017 Jan;109(1):16-26. doi: 10.1016/j.ygeno.2016.11.008. Epub 2016 Nov 29.
2
Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury.干细胞衍生模型用于增进对人类药物性肝损伤机制的理解和预测。
Hepatology. 2017 Feb;65(2):710-721. doi: 10.1002/hep.28886. Epub 2016 Nov 30.
3
Laminin-511 and laminin-521-based matrices for efficient hepatic specification of human pluripotent stem cells.基于层粘连蛋白-511 和层粘连蛋白-521 的基质促进人多能干细胞向肝系细胞的高效特化
Biomaterials. 2016 Oct;103:86-100. doi: 10.1016/j.biomaterials.2016.06.054. Epub 2016 Jun 23.
4
Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes.重组层粘连蛋白驱动 hESC 来源的肝细胞的分化和自组织。
Stem Cell Reports. 2015 Dec 8;5(6):1250-1262. doi: 10.1016/j.stemcr.2015.10.016. Epub 2015 Nov 25.
5
A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs.对基因匹配的细胞系进行比较，结果显示人类诱导多能干细胞（iPSC）与胚胎干细胞（ESC）具有等效性。
Nat Biotechnol. 2015 Nov;33(11):1173-81. doi: 10.1038/nbt.3388. Epub 2015 Oct 26.
6
Polarisation and functional characterisation of hepatocytes derived from human embryonic and mesenchymal stem cells.源自人类胚胎干细胞和间充质干细胞的肝细胞的极化与功能特性分析
Biomed Rep. 2015 Sep;3(5):626-636. doi: 10.3892/br.2015.480. Epub 2015 Jun 18.
7
Cost-effective differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.使用小分子实现人多能干细胞来源的类肝细胞的经济有效分化。
Biomaterials. 2015 Nov;70:115-25. doi: 10.1016/j.biomaterials.2015.08.002. Epub 2015 Aug 4.
8
Polyurethane: Stable Cell Phenotype Requires Plasticity: Polymer Supported Directed Differentiation Reveals a Unique Gene Signature Predicting Stable Hepatocyte Performance (Adv. Healthcare Mater. 12/2015).聚氨酯：稳定的细胞表型需要可塑性：聚合物支持的定向分化揭示了一个独特的基因特征，可预测稳定的肝细胞性能（Adv. Healthcare Mater. 12/2015）。
Adv Healthc Mater. 2015 Aug 26;4(12):1819. doi: 10.1002/adhm.201570072.
9
Serum-Free Directed Differentiation of Human Embryonic Stem Cells to Hepatocytes.人胚胎干细胞向肝细胞的无血清定向分化
Methods Mol Biol. 2015;1250:105-11. doi: 10.1007/978-1-4939-2074-7_7.
10
Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism.血液单核细胞的高效附加型重编程及向具有功能性药物代谢的肝细胞分化。
Exp Cell Res. 2015 Nov 1;338(2):203-13. doi: 10.1016/j.yexcr.2015.08.004. Epub 2015 Aug 6.
Zotero 插件