Zhang Stephanie, Markey Miles, Pena Caroline D, Venkatesh Tadmiri, Vazquez Maribel
Department of Biomedical Engineering, Binghamton University, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA.
Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, NJ 08854, USA.
Micromachines (Basel). 2020 Mar 31;11(4):363. doi: 10.3390/mi11040363.
Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes of replacement neural stem cells. The system scales with the microstructure of the Drosophila optic stalk, which is a pre-cursor to the optic nerve, to produce signaling fields spatially comparable to in vivo RNB stimuli. Experiments used the micro-optic stalk system, or μOS, to demonstrate the preferred sizing and directional migration of collective, motile RNB groups in response to changes in exogenous concentrations of fibroblast growth factor (FGF), which is a key factor in development. Our data highlight the importance of cell-to-cell contacts in enabling cell cohesion during collective RNB migration and point to the unexplored synergy of invertebrate cell study and microfluidic platforms to advance regenerative strategies.
当代再生疗法引入了类干细胞,通过重现眼睛发育的关键过程来替代视觉系统中受损的神经元。神经干细胞的集体迁移是视网膜生成的基础,并且利用果蝇模型对其进行了深入研究。然而,尽管视网膜成神经细胞(RNBs)的迁移行为对这个无脊椎动物模型的视网膜发育至关重要,但令人惊讶的是,对其研究却很少。当前项目开发了一种新的微流体系统,以检查从果蝇发育中的视觉系统中提取的RNBs的集体迁移,作为替代神经干细胞集体运动过程的模型。该系统与视神经的前身果蝇视柄的微观结构相匹配,以产生在空间上与体内RNB刺激相当的信号场。实验使用微视柄系统(μOS)来证明集体运动的RNB群体在响应成纤维细胞生长因子(FGF)外源性浓度变化时的优选大小和定向迁移,FGF是发育中的关键因子。我们的数据强调了细胞间接触在集体RNB迁移过程中实现细胞黏附的重要性,并指出了无脊椎动物细胞研究与微流体平台在推进再生策略方面尚未探索的协同作用。