Emerging therapies have begun to evaluate the abilities of Müller glial cells (MGCs) to protect and/or regenerate neurons following retina injury. The migration of donor cells is central to many reparative strategies, where cells must achieve appropriate positioning to facilitate localized repair. Although chemical cues have been implicated in the MGC migratory responses of numerous retinopathies, MGC-based therapies have yet to explore the extent to which external biochemical stimuli can direct MGC behavior. The current study uses a microfluidics-based assay to evaluate the migration of cultured rMC-1 cells (as model MGC) in response to quantitatively-controlled microenvironments of signaling factors implicated in retinal regeneration: basic Fibroblast Growth factor (bFGF or FGF2); Fibroblast Growth factor 8 (FGF8); Vascular Endothelial Growth Factor (VEGF); and Epidermal Growth Factor (EGF). Findings indicate that rMC-1 cells exhibited minimal motility in response to FGF2, FGF8 and VEGF, but highly-directional migration in response to EGF. Further, the responses were blocked by inhibitors of EGF-R and of the MAPK signaling pathway. Significantly, microfluidics data demonstrate that changes in the EGF gradient (i.e. change in EGF concentration over distance) resulted in the directional chemotactic migration of the cells. By contrast, small increases in EGF concentration, alone, resulted in non-directional cell motility, or chemokinesis. This microfluidics-enhanced approach, incorporating the ability both to modulate and asses the responses of motile donor cells to a range of potential chemotactic stimuli, can be applied to potential donor cell populations obtained directly from human specimens, and readily expanded to incorporate drug-eluting biomaterials and combinations of desired ligands.

中文翻译：

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控制微环境以评估培养的Müller胶质细胞的趋化特性。

新兴疗法已经开始评估穆勒神经胶质细胞（MGC）在视网膜损伤后保护和/或再生神经元的能力。供体细胞的迁移是许多修复策略的核心，其中细胞必须实现适当的定位以促进局部修复。尽管化学提示已与多种视网膜病变的MGC迁移反应有关，但基于MGC的疗法尚未探索外部生化刺激可指导MGC行为的程度。当前的研究使用基于微流体的分析方法来评估培养的rMC-1细胞（作为MGC模型）的迁移，以响应涉及视网膜再生的信号控制因子的定量控制微环境：碱性成纤维细胞生长因子（bFGF或FGF2）；成纤维细胞生长因子8（FGF8）；血管内皮生长因子（VEGF）；和表皮生长因子（EGF）。结果表明，rMC-1细胞对FGF2，FGF8和VEGF的反应显示出最小的运动能力，但对EGF的反应却具有高度的方向性。此外，该反应被EGF-R和MAPK信号通路的抑制剂所阻断。重要的是，微流体数据表明EGF梯度的变化（即EGF浓度随距离的变化）导致了细胞的定向趋化迁移。相比之下，单独增加EGF的浓度会导致无方向性的细胞运动或趋化因子。这种微流控增强方法结合了调节和评估活动性供体细胞对一系列潜在趋化性刺激的反应的能力，