Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels
Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels
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DOI：
10.1002/sctm.19-0159
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发表时间：
2019-12-01
影响因子：
6
通讯作者：
Lo, Eng H.
中科院分区：
文献类型：
--
作者：
Chan, Su Jing;Niu, Wanting;Lo, Eng H.
生物材料提供了新的平台来提供用于中枢神经系统（CNS）修复的干细胞和生长因子疗法。这些方法大多数都集中在促进神经祖细胞和神经发生。然而，现在人们越来越认识到神经胶质反应对于整个神经血管单元的恢复至关重要。在这项研究中，我们研究了含有表皮生长因子（EGF）的水凝胶对原代星形胶质细胞培养物的细胞影响。单独的 EGF 和 EGF-水凝胶都同样促进星形胶质细胞增殖，但 EGF-水凝胶进一步增强了星形胶质细胞的活化，胶质纤维酸性蛋白 (GFAP) 基因表达显着升高证明了这一点。此后，由 EGF-水凝胶激活的星形胶质细胞的条件培养基可保护神经元免受损伤，并在氧糖剥夺后促进突触可塑性。总而言之，这些发现表明 EGF-水凝胶可以将星形胶质细胞转变为神经支持表型。与这一观点一致的是，定量聚合酶链式反应 (qPCR) 表明，EGF 水凝胶部分通过下调潜在负面 A1 样基因（Fbln5 和 Rt1-S3）和上调潜在有益 A2 样基因（Clcf1、Tgm1 和 Ptgs2）来改变星形胶质细胞。有必要进一步研究探索使用生物材料改变星形胶质细胞行为的想法，从而在中枢神经系统干细胞和生长因子治疗的背景下间接增强神经保护和神经可塑性。干细胞转化医学2019;8:1242&1248
Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit. In this study, we investigated the cellular effects of epidermal growth factor (EGF) containing hydrogels on primary astrocyte cultures. Both EGF alone and EGF-hydrogel equally promoted astrocyte proliferation, but EGF-hydrogels further enhanced astrocyte activation, as evidenced by a significantly elevated Glial fibrillary acidic protein (GFAP) gene expression. Thereafter, conditioned media from astrocytes activated by EGF-hydrogel protected neurons against injury and promoted synaptic plasticity after oxygen-glucose deprivation. Taken together, these findings suggest that EGF-hydrogels can shift astrocytes into neuro-supportive phenotypes. Consistent with this idea, quantitative-polymerase chain reaction (qPCR) demonstrated that EGF-hydrogels shifted astrocytes in part by downregulating potentially negative A1-like genes (Fbln5 and Rt1-S3) and upregulating potentially beneficial A2-like genes (Clcf1, Tgm1, and Ptgs2). Further studies are warranted to explore the idea of using biomaterials to modify astrocyte behavior and thus indirectly augment neuroprotection and neuroplasticity in the context of stem cell and growth factor therapies for the CNS. Stem Cells Translational Medicine 2019;8:1242&1248