Department of Molecular Biology, Ariel University †, Ariel, 40700, Israel.
Biomed Mater. 2019 Apr 29;14(4):045005. doi: 10.1088/1748-605X/ab0d69.
Astrogilosis is the response of astrocytes to brain trauma which manifest opposite roles on brain injury repair. On the one hand, astrocytes undergoing astrogliosis inhibit tissue regeneration by forming scar tissue, but, on the other hand, they enhance damage repair through secretion of neuro-protecting and neurotrophic factors. Therefore, identifying means that regulate astrogliosis can provide a control over progression and repair of brain damage. We have previously shown that the calcium carbonate skeleton of corals upregulates two manifestations of astrogliosis in astrocytes in culture-expression of the Glial Fibrillay Acidic Protein (GFAP), and shape conversion from non-spiky to reactive spiky cell morphology. Here, we investigated if the surface topography of the coralline skeleton plays a role in GFAP expression and the morphogenesis of reactive astrocytes. To address that, we utilized the non-porous exoskeleton of the coral Trachyphyllia geoffroyi, having three topographies of distinct heights on its surface: rough surface (made of <30 μm height bumps), protrusions (50-250 μm) and ridges (>250 μm). We observed that astrocytes reacted similarly to all three structures in terms of adhesion, acquisition of a spiky morphology and organization in networks. By contrast, the extent by which these cells expressed GFAP was structure-dependent. The expression was 2-fold higher on protrusions and ridges than on the rough surface and acquired. Accordingly, the distribution pattern of the GFAP overexpressing astrocytes followed that of the protrusions and ridges. Hence, fabricating coralline scaffolds with designed flatness/protrusions/ridges ratios can serve to control astrogliosis-derived regeneration in TBI wounds, and as a result improve the capacity to repair brain damage.
星形胶质细胞增生是星形胶质细胞对脑创伤的反应,它在脑损伤修复中表现出相反的作用。一方面,星形胶质细胞增生会通过形成瘢痕组织来抑制组织再生,但另一方面,它们通过分泌神经营养和神保护因子来增强损伤修复。因此,确定调节星形胶质细胞增生的方法可以控制脑损伤的进展和修复。我们之前已经表明,珊瑚的碳酸钙骨架上调了培养中的星形胶质细胞的两种星形胶质细胞增生表现——胶质纤维酸性蛋白(GFAP)的表达,以及从非刺状到反应性刺状细胞形态的形状转换。在这里,我们研究了珊瑚质骨架的表面形貌是否在 GFAP 表达和反应性星形胶质细胞的形态发生中起作用。为了解决这个问题,我们利用了珊瑚 Trachyphyllia geoffroyi 的非多孔外壳,其表面具有三种不同高度的形貌:粗糙表面(由<30 μm 高度的凸起组成)、凸起(50-250 μm)和脊(>250 μm)。我们观察到,星形胶质细胞在粘附、获得刺状形态和网络组织方面对所有三种结构的反应相似。相比之下,这些细胞表达 GFAP 的程度取决于结构。在凸起和脊上的表达是粗糙表面的 2 倍,并且获得了更高的表达。因此,过度表达 GFAP 的星形胶质细胞的分布模式遵循凸起和脊的分布模式。因此,制造具有设计的平整度/凸起/脊比的珊瑚质支架可以用于控制创伤性脑损伤(TBI)伤口中的星形胶质细胞增生衍生的再生,并提高修复脑损伤的能力。