Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: Hepatocytes cultured in a sandwich configuration

Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: Hepatocytes cultured in a sandwich configuration
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DOI:
10.1096/fasebj.10.13.8940293
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发表时间:
1996-11-01
期刊:
影响因子:
4.8
通讯作者:
Yarmush, ML
Yarmush, ML
中科院分区:
生物学2区
文献类型:
--
作者:
Berthiaume, F;Moghe, PV;Yarmush, ML

文献摘要

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细胞外基质(ECM)几何形状是细胞极性和功能的重要调节剂。例如,3维基质通常比传统的2维基质更有效地诱导分化的细胞功能。ECM拓扑结构的影响可以使用一种技术以受控的方式进行研究,其中在单个表面上培养的细胞被第二层ECM覆盖,从而产生“三明治”构型,以这种方式覆盖的上皮或内皮细胞的汇合单层通常重组成使人想起其天然组织的结构。在肝细胞的情况下,覆盖导致细胞骨架的显著重组,采用体内样形态和极性,和表达多种肝脏特异性功能。在这篇简短的综述中,我们使用夹心肝细胞培养系统来说明ECM几何形状对细胞功能的影响,在定义这种培养系统作为研究肝组织生理学和形态发生的体外模型的平行性、优势和局限性的背景下总结了相关研究,我们还探索了它作为研究肝脏药理学和毒理学的模型的一些潜在用途。以及肝脏保存技术和肝脏辅助装置的开发。
Extracellular matrix (ECM) geometry is an important modulator of cell polarity and function, For example, 3-dimensional matrices often more effectively induce differentiated cell function than traditional 2-dimensional substrates, The effect of ECM topology can be investigated in a controlled fashion using a technique whereby cells cultured on a single surface are overlaid with a second layer of ECM, thereby creating a ''sandwich'' configuration, Confluent monolayers of epithelial or endothelial cells overlaid in this fashion often reorganize into structures that are reminiscent of their native tissue, In the case of hepatocytes, the overlay causes a dramatic reorganization of the cytoskeleton, adoption of in vivo-like morphology and polarity, and expression of a wide array of liver-specific functions. In this short review, we use the sandwiched hepatocyte culture system to illustrate the effect of ECM geometry on cellular function, Pertinent studies are summarized in the context of defining the parallels, strengths, and Limitations of this culture system as an in vitro model to study the physiology and morphogenesis of liver tissue, We also explore some of its a potential uses as a model to study liver pharmacology and toxicology, and for the development of Liver preservation techniques and liver-assist devices.