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人诱导多能干细胞来源的确定内胚层扩增与肝脏分化。

Human-Induced Pluripotent Stem Cell-Derived Definitive Endoderm Bulk Up and Hepatic Differentiation.

作者信息

Palakkan Anwar A, Nanda Jyoti, Ross James A

机构信息

Tissue Injury and Repair Group, Chancellor's Building, University of Edinburgh, Edinburgh, UK.

Immunology & Stem Cell Biology, Aravind Medical Research Foundation, Madurai, Tamil Nadu, India.

出版信息

Methods Mol Biol. 2025;2924:31-43. doi: 10.1007/978-1-0716-4530-7_3.

DOI:10.1007/978-1-0716-4530-7_3
PMID:40307633
Abstract

We have developed a method to bulk up definitive endoderm cells generated from human iPSC, and can be further differentiated to hepatocytes. Human iPSC-derived definitive endoderm cells were sorted, based on the expression of CXCR4, and were able to proliferate for extended periods and can be cryopreserved. These cells were able to generate functional hepatocytes expressing albumin and alpha-fetoprotein in different multi-well formats. This method would help to produce more consistent hepatocytes and also enable the development of high throughput screening strategies.

摘要

我们已经开发出一种方法来扩增从人诱导多能干细胞(iPSC)生成的定形内胚层细胞,并且这些细胞能够进一步分化为肝细胞。基于CXCR4的表达对人iPSC衍生的定形内胚层细胞进行分选,这些细胞能够长期增殖并且可以冷冻保存。这些细胞能够在不同的多孔板形式中生成表达白蛋白和甲胎蛋白的功能性肝细胞。这种方法将有助于产生更一致的肝细胞,还能推动高通量筛选策略的发展。

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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.
2
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本文引用的文献

1
Comparative transcriptomic and phenotypic analysis of induced pluripotent stem cell hepatocyte-like cells and primary human hepatocytes.诱导多能干细胞肝细胞样细胞与原代人肝细胞的比较转录组学和表型分析。
Cell Tissue Res. 2024 Apr;396(1):119-139. doi: 10.1007/s00441-024-03868-9. Epub 2024 Feb 19.
2
Human iPSC-derived hepatocytes in 2D and 3D suspension culture for cryopreservation and in vitro toxicity studies.二维和三维悬浮培养的人诱导多能干细胞衍生的肝细胞用于低温保存和体外毒性研究。
Reprod Toxicol. 2022 Aug;111:68-80. doi: 10.1016/j.reprotox.2022.05.005. Epub 2022 May 20.
3
Stem cell-derived polarized hepatocytes.
干细胞来源的极化肝细胞。
Nat Commun. 2020 Apr 3;11(1):1677. doi: 10.1038/s41467-020-15337-2.
4
iPSC-Derived Hepatocytes as a Platform for Disease Modeling and Drug Discovery.诱导多能干细胞衍生的肝细胞作为疾病建模和药物发现的平台。
Front Med (Lausanne). 2019 Nov 15;6:265. doi: 10.3389/fmed.2019.00265. eCollection 2019.
5
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.
6
Scalable Differentiation of Human iPSCs in a Multicellular Spheroid-based 3D Culture into Hepatocyte-like Cells through Direct Wnt/β-catenin Pathway Inhibition.通过直接 Wnt/β-catenin 通路抑制,在基于多细胞球体的 3D 培养物中可扩展地将人诱导多能干细胞分化为肝样细胞。
Sci Rep. 2016 Sep 12;6:32888. doi: 10.1038/srep32888.
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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.
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Liver tissue engineering and cell sources: issues and challenges.肝脏组织工程和细胞来源:问题与挑战。
Liver Int. 2013 May;33(5):666-76. doi: 10.1111/liv.12134. Epub 2013 Mar 15.
9
Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling.将人胚胎干细胞高效分化为功能性肝内胚层需要激活素A和Wnt3a信号。
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12301-6. doi: 10.1073/pnas.0806522105. Epub 2008 Aug 21.