Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
Molecular Proteomics Laboratory, Biologisch-Medizinisches Forschungszentrum, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany.
Biomaterials. 2018 Oct;180:36-51. doi: 10.1016/j.biomaterials.2018.07.008. Epub 2018 Jul 7.
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.
层粘连蛋白α5 蛋白链是基底膜的组成部分,对维持干细胞至关重要。肝星状细胞(HSC)是肝内间充质干细胞,位于 Disse 间隙的基底膜样结构中处于静止状态。在本研究中,正常大鼠肝 Disse 间隙中检测到层粘连蛋白α5 链。由于 HSC 对肝再生至关重要,并可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,并更好地保留了它们的视黄醇储存以及静止和干细胞相关表型,而 PS/LN-211 或 PS 上的 HSC 则分化为肌成纤维细胞样细胞。为了改善层粘连蛋白分子在 HSC 培养表面上的均匀性和呈现方式,生成了层粘连蛋白功能化的金纳米结构玻璃表面。这种方法进一步增强了 HSC 中静止相关基因的表达。总之,这些结果表明 LN-521 支持 HSC 的静止状态,并且层粘连蛋白α5 可以被视为 Disse 间隙中其生态位的重要组成部分。