Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes.
Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes.
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DOI：
10.1155/2016/5481493
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发表时间：
2016
影响因子：
4.3
通讯作者：
Amicone L
中科院分区：
文献类型：
--
作者：
Cozzolino AM;Noce V;Battistelli C;Marchetti A;Grassi G;Cicchini C;Tripodi M;Amicone L
在许多细胞类型中，几种细胞过程，如干细胞/前体细胞的分化、分化表型的维持、运动性、粘附性、生长和存活，严格依赖于细胞外基质的硬度，所述细胞外基质在体内表征其相应器官和组织。在肝脏中，基质硬度对于获得正确的器官生理学是必不可少的，而任何改变都会导致肝细胞功能障碍。基质的刚性对于几种细胞类型的培养来说是一个不可忽略的因素，因此，迄今为止获得的许多数据，其中细胞在塑料上培养，可以进行修改。关于肝细胞，标准培养条件导致原代肝细胞的去分化、星状细胞转分化成肌成纤维细胞和窦状内皮的开窗功能丧失。此外，肝干细胞/前体细胞的标准培养阻碍了上皮细胞/肝细胞分化程序的有效执行，导致仅部分表达肝功能和产物的细胞群的扩增。克服这些限制是强制性的任何方法的肝组织工程。在这里，我们提出了细胞系作为肝干细胞和肝细胞的体外模型，并提出了一种创新的培养方法，该方法考虑到基质硬度，以分别获得快速有效的分化过程和维持完全分化的表型。
In many cell types, several cellular processes, such as differentiation of stem/precursor cells, maintenance of differentiated phenotype, motility, adhesion, growth, and survival, strictly depend on the stiffness of extracellular matrix that, in vivo, characterizes their correspondent organ and tissue. In the liver, the stromal rigidity is essential to obtain the correct organ physiology whereas any alteration causes liver cell dysfunctions. The rigidity of the substrate is an element no longer negligible for the cultivation of several cell types, so that many data so far obtained, where cells have been cultured on plastic, could be revised. Regarding liver cells, standard culture conditions lead to the dedifferentiation of primary hepatocytes, transdifferentiation of stellate cells into myofibroblasts, and loss of fenestration of sinusoidal endothelium. Furthermore, standard cultivation of liver stem/precursor cells impedes an efficient execution of the epithelial/hepatocyte differentiation program, leading to the expansion of a cell population expressing only partially liver functions and products. Overcoming these limitations is mandatory for any approach of liver tissue engineering. Here we propose cell lines as in vitro models of liver stem cells and hepatocytes and an innovative culture method that takes into account the substrate stiffness to obtain, respectively, a rapid and efficient differentiation process and the maintenance of the fully differentiated phenotype.