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使用优化的合成表面稳定肝细胞表型。

Stabilizing hepatocellular phenotype using optimized synthetic surfaces.

作者信息

Lucendo-Villarin Baltasar, Cameron Kate, Szkolnicka Dagmara, Travers Paul, Khan Ferdous, Walton Jeffrey G, Iredale John, Bradley Mark, Hay David C

机构信息

MRC Centre for Regenerative Medicine, University of Edinburgh.

School of Chemistry, University of Edinburgh.

出版信息

J Vis Exp. 2014 Sep 26(91):51723. doi: 10.3791/51723.

DOI:10.3791/51723
PMID:25285607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4828135/
Abstract

Currently, one of the major limitations in cell biology is maintaining differentiated cell phenotype. Biological matrices are commonly used for culturing and maintaining primary and pluripotent stem cell derived hepatocytes. While biological matrices are useful, they permit short term culture of hepatocytes, limiting their widespread application. We have attempted to overcome the limitations using a synthetic polymer coating. Polymers represent one of the broadest classes of biomaterials and possess a wide range of mechanical, physical and chemical properties, which can be fine-tuned for purpose. Importantly, such materials can be scaled to quality assured standards and display batch-to-batch consistency. This is essential if cells are to be expanded for high through-put screening in the pharmaceutical testing industry or for cellular based therapy. Polyurethanes (PUs) are one group of materials that have shown promise in cell culture. Our recent progress in optimizing a polyurethane coated surface, for long-term culture of human hepatocytes displaying stable phenotype, is presented and discussed.

摘要

目前,细胞生物学的主要局限之一是维持分化细胞的表型。生物基质常用于培养和维持原代及多能干细胞来源的肝细胞。虽然生物基质很有用,但它们只能对肝细胞进行短期培养,限制了其广泛应用。我们试图通过使用合成聚合物涂层来克服这些限制。聚合物是种类最为繁多的生物材料之一,具有广泛的机械、物理和化学性质,可根据需要进行微调。重要的是,此类材料可以按质量保证标准进行规模化生产,并显示出批次间的一致性。如果要在制药测试行业进行高通量筛选或基于细胞的治疗而扩大细胞规模,这一点至关重要。聚氨酯(PU)是一类在细胞培养中显示出前景的材料。本文展示并讨论了我们在优化聚氨酯涂层表面以长期培养具有稳定表型的人肝细胞方面的最新进展。

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Developing defined substrates for stem cell culture and differentiation.开发用于干细胞培养和分化的定义明确的基质。
Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). doi: 10.1098/rstb.2017.0230.

本文引用的文献

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Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment.在无动物成分的定义环境中,利用层粘连蛋白 521/上皮钙黏蛋白基质对人胚胎干细胞进行克隆培养。
Nat Commun. 2014;5:3195. doi: 10.1038/ncomms4195.
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Accurate prediction of drug-induced liver injury using stem cell-derived populations.利用干细胞衍生群体准确预测药物性肝损伤。
Stem Cells Transl Med. 2014 Feb;3(2):141-8. doi: 10.5966/sctm.2013-0146. Epub 2013 Dec 27.
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Developing high-fidelity hepatotoxicity models from pluripotent stem cells.从多能干细胞中开发高保真度的肝毒性模型。
Stem Cells Transl Med. 2013 Jul;2(7):505-9. doi: 10.5966/sctm.2012-0138. Epub 2013 Jun 11.
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Maintaining hepatic stem cell gene expression on biological and synthetic substrata.在生物和合成基质上维持肝干细胞基因表达。
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A thermoresponsive and chemically defined hydrogel for long-term culture of human embryonic stem cells.一种热响应且化学成分明确的水凝胶,可用于人类胚胎干细胞的长期培养。
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Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate.硅酸取代的磷酸钙对人骨髓间充质干细胞/前体细胞的定向成骨分化作用。
J Biomed Mater Res A. 2013 Jan;101(1):13-22. doi: 10.1002/jbm.a.34261. Epub 2012 Jun 26.
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SUMOylation of HNF4α regulates protein stability and hepatocyte function.SUMOylation 修饰调控 HNF4α 的蛋白稳定性和肝细胞功能。
J Cell Sci. 2012 Aug 1;125(Pt 15):3630-5. doi: 10.1242/jcs.102889. Epub 2012 Apr 14.
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