Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on micropatterned polymer substrates.
Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on micropatterned polymer substrates.
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来自新皮质星形胶质细胞的可溶性因子增强了成年大鼠海马神经祖细胞在微图案聚合物基底上的神经元分化。
DOI：
10.1002/jbm.a.32242
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Sakaguchi,DonaldS
中科院分区：
文献类型：
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作者：
Oh,Jisun;Recknor,JenniferB;Recknor,JustinC;Mallapragada,SuryaK;Sakaguchi,DonaldS
成年大鼠海马祖细胞 (AHPC) 是自我更新的多能神经祖细胞，具有分化为神经元和神经胶质细胞的能力。之前，我们证明 AHPC 与出生后第 2 天的 1 型皮质星形胶质细胞在层粘连蛋白包被的微图案聚合物基质上共培养有利于 AHPC 的选择性神经元分化（Recknor 等人，Biomaterials 2006；27：4098–4108）。在这种情况下，多维细胞-细胞和/或细胞-细胞外基质相互作用，以及星形胶质细胞释放的可能的可溶性因子提供了空间和时间控制，选择性地增强同一基质的不同地形区域上的神经元分化和神经突排列。为了研究星形胶质细胞衍生的可溶性因子作为参与神经元分化的线索的潜在作用，使用了非接触式共培养系统。在对照条件下，14% 的 AHPC 对神经元标记物 III 类 b 微管蛋白 (TUJ1-IR) 具有免疫反应性 (IR)。当与星形胶质细胞物理接触共培养时，神经元分化显着增加至约 25%，与我们之前的结果一致。此外，在使用 Transwell® 插入培养物的非接触共培养条件下，神经元分化显着增加至 64%。此外，与非接触共培养条件下的非图案化平面基底相比，图案化基底上的神经元细胞体的神经突生长要大得多。综上所述，我们的结果表明，星形胶质细胞衍生的可溶性因子为在微图案基质上培养的 AHPC 的特定神经元分化提供了线索。此外，对神经元分化的抑制影响似乎是通过与共培养的星形胶质细胞接触介导的。这些结果为控制神经祖细胞/干细胞分化的机制提供了重要的见解，并促进中枢神经系统修复策略的制定。 Ó 2008 Wiley periodicals, Inc. J Biomed Mater Res 91A: 575–585, 2009
Rat adult hippocampal progenitor cells (AHPCs) are self-renewing, multipotent neural progenitors that have the ability to differentiate into neurons and glia. Previously, we demonstrated that coculture of AHPCs with postnatal day 2, type 1 cortical astrocytes on laminin-coated micropatterned polymer substrates facilitates selective neuronal differentiation of the AHPCs (Recknor et al., Biomaterials 2006; 27: 4098–4108). Under this condition, multidimensional cell–cell and/or cell–extracellular matrix interactions, as well as possible soluble factors released from astrocytes provided spatial and temporal control selectively enhancing neuronal differentiation and neurite alignment on topographically different regions of the same substrate. To investigate the potential role of astrocyte-derived soluble factors as cues involved in neuronal differentiation, a noncontact coculture system was used. Under control conditions, 14% of the AHPCs were immunoreactive (IR) for the neuronal marker, class III b-tubulin (TUJ1-IR). When cocultured in physical contact with astrocytes, neuronal differentiation increased significantly to about 25%, consistent with our previous results. Moreover, under noncontact coculture conditions using Transwell® insert cultures, neuronal differentiation was dramatically increased to 64%. Furthermore, neurite outgrowth from neuronal cell bodies was considerably greater on the patterned substrate when compared with the nonpatterned planar substrate under noncontact coculture conditions. Taken together, our results demonstrate that astrocyte-derived soluble factors provide cues for specific neuronal differentiation of AHPCs cultured on micropatterned substrates. In addition, a suppressive influence on neuronal differentiation appears to be mediated by contact with cocultured astrocytes. These results provide important insights into mechanisms for controlling neural progenitor/stem cell differentiation and facilitate development of strategies for CNS repair. Ó 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 575–585, 2009