Engineering cell-material interfaces for long-term expansion of human pluripotent stem cells.

Engineering cell-material interfaces for long-term expansion of human pluripotent stem cells.
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工程细胞材料界面,用于人类多能干细胞长期扩张。

DOI:
10.1016/j.biomaterials.2012.10.020
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发表时间:
2013-01
期刊:
影响因子:
14
通讯作者:
Varghese S
Varghese S
中科院分区:
工程技术1区
文献类型:
--
作者:
Chang CW;Hwang Y;Brafman D;Hagan T;Phung C;Varghese S

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支持人类多能干细胞(HPSCs)长期扩增的低成本、可扩展的合成基质有许多应用,从药物筛选平台到再生医学。在这里,我们报告了一种基于水凝胶的基质的开发,该基质含有合成的类似肝素的部分,支持hPSC(≥20代)在化学定义的介质中的长期扩张。在此合成基质上扩增的hPSCs保持了其特有的形态、集落形成能力、核型稳定性和分化潜能。我们还以合成的基质为平台,研究了细胞外环境的各种物理化学性质对hPSCs的黏附、生长和自我更新的影响。观察到的细胞反应可以用基质界面介导的细胞外基质蛋白、生长因子和其他细胞分泌因子的结合来解释,这为hPSCs的自我更新创造了一个有益的微环境。这些合成基质由现成的成分组成,很容易合成,为阐明控制干细胞命运的分子机制提供了理想的工具。
Cost-effective and scalable synthetic matrices that support long-term expansion of human pluripotent stem cells (hPSCs) have many applications, ranging from drug screening platforms to regenerative medicine. Here, we report the development of a hydrogel-based matrix containing synthetic heparin-mimicking moieties that supports the long-term expansion of hPSCs (≥20 passages) in a chemically defined medium. HPSCs expanded on this synthetic matrix maintained their characteristic morphology, colony forming ability, karyotypic stability, and differentiation potential. We also used the synthetic matrix as a platform to investigate the effects of various physicochemical properties of the extracellular environment on the adhesion, growth, and self-renewal of hPSCs. The observed cellular responses can be explained in terms of matrix interface-mediated binding of extracellular matrix proteins, growth factors, and other cell secreted factors, which create an instructive microenvironment to support self-renewal of hPSCs. These synthetic matrices, which comprise of “off-the-shelf” components and are easy to synthesize, provide an ideal tool to elucidate the molecular mechanisms that control stem cell fate.
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发表时间: 2010-12-13
期刊: Biomacromolecules
影响因子: 6.2
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影响因子: 11.1
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通讯作者: Voldman, Joel