PDF(Pubmed)
Abstract：
Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood-brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system.
摘要：
星形胶质细胞在中枢神经系统中发挥重要作用,有助于突触的发育和维持，神经递质的循环利用，以及血脑屏障的完整性和功能。星形胶质细胞也与各种神经退行性疾病的病理生理学有关。星形胶质细胞的功能和组织受到细胞外基质（ECM）介导的相互作用的严格调节。工程化的水凝胶可以模拟ECM的关键方面，并且可以对控制星形胶质细胞行为的ECM相关因子进行系统研究。在这项研究中,我们使用模块化的基于透明质酸的水凝胶系统探索神经母细胞瘤(SH-SY5Y)和胶质母细胞瘤(U87)细胞系与人胎儿原代星形胶质细胞(FPA)之间的相互作用.形态学分析揭示,与细胞系相比,FPA与基于透明质酸的凝胶具有更高程度的相互作用。这种相互作用通过细胞粘附肽(cRGD和IKVAV)与透明质酸主链的缀合而增强。这些效果在3D生物打印的结构中保留并显著。使用cRGD官能化透明质酸的生物打印的FPA显示出广泛且明确的突起以及相邻细胞之间的多个连接。定制和优化星形胶质细胞相容性ECM模拟水凝胶的可能性，这些水凝胶可以通过增材生物制造进行处理，可以促进中枢神经系统高级组织和疾病模型的发展。
