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Laminin-521 promotes quiescence in isolated stellate cells from rat liver
Biomaterials ( IF 14.0 ) Pub Date : 2018-07-07 , DOI: 10.1016/j.biomaterials.2018.07.008
Friederike Rohn , Claus Kordes , Mirco Castoldi , Silke Götze , Gereon Poschmann , Kai Stühler , Diran Herebian , Amelie S. Benk , Fania Geiger , Tingyu Zhang , Joachim P. Spatz , Dieter Häussinger

The laminin α5 protein chain is an element of basement membranes and important to maintain stem cells. Hepatic stellate cells (HSC) are liver-resident mesenchymal stem cells, which reside in a quiescent state on a basement membrane-like structure in the space of Dissé. In the present study, laminin α5 chain was detected in the space of Dissé of normal rat liver. Since HSC are critical for liver regeneration and can contribute to fibrosis in chronic liver diseases, the effect of laminins on HSC maintenance was investigated. Therefore, isolated rat HSC were seeded on uncoated polystyrene (PS) or PS coated with either laminin-521 (PS/LN-521) or laminin-211 (PS/LN-211). PS/LN-521 improved HSC adhesion and better preserved their retinoid stores as well as quiescence- and stem cell-associated phenotype, whereas HSC on PS/LN-211 or PS developed into myofibroblasts-like cells. To improve the homogeneity as well as the presentation of laminin molecules on the culture surface to HSC, laminin-functionalized, gold-nanostructured glass surfaces were generated. This approach further enhanced the expression of quiescence-associated genes in HSC. In conclusion, the results indicate that LN-521 supports the quiescent state of HSC and laminin α5 can be regarded as an important element of their niche in the space of Dissé.



中文翻译:

Laminin-521促进大鼠肝脏分离的星状细胞中的静止

层粘连蛋白α5蛋白链是基底膜的一个元素,对维持干细胞很重要。肝星状细胞(HSC)是驻留于肝脏的间充质干细胞,在Dissé空间中以静止状态驻留在基底膜样结构上。在本研究中,在正常大鼠肝脏的Dissé空间中检测到层粘连蛋白α5链。由于HSC对肝再生至关重要,并且可以导致慢性肝病中的纤维化,因此研究了层粘连蛋白对HSC维持的影响。因此,将分离的大鼠HSC接种在未涂覆的聚苯乙烯(PS)或涂覆有层粘连蛋白521(PS / LN-521)或层粘连蛋白211(PS / LN-211)的PS上。PS / LN-521改善了HSC的黏附力,并更好地保留了它们的类维生素A储存以及静止和干细胞相关的表型,而PS / LN-211或PS上的HSC则发展为成肌纤维细胞样细胞。为了提高均一性以及层粘连蛋白分子在培养表面上对HSC的呈递,生成了层粘连蛋白功能化的金纳米结构玻璃表面。该方法进一步增强了HSC中静止相关基因的表达。总之,结果表明LN-521支持HSC的静止状态,层粘连蛋白α5可以被视为在Dissé空间中其利基的重要元素。

更新日期:2018-07-08
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