Innovations in Surfaces, Materials and Related Technologies (iSMART), College of Science and Technology, Nottingham Trent University, Clifton, NG11 8NS, UK.
Interdisciplinary Biomedical Research Centre (IBRC), College of Science and Technology, Nottingham Trent University, Clifton, NG11 8NS, UK.
Sci Rep. 2020 Feb 17;10(1):2767. doi: 10.1038/s41598-020-59310-x.
Current therapeutic strategies for Parkinson's disease (PD) aim to delay progression or replace damaged neurons by restoring the original neuronal structures. The poor regenerative capacity of neural tissue highlights the need for the development of cellular environments to model the pathogenesis of PD. In the current work, we have characterised the growth, survival and response to PD mimetics of human SH-SY5Y neuroblastoma and U-87MG glioblastoma cell lines cultured on polyacrylonitrile (PAN) and Jeffamine® doped polyacrylonitrile (PJ) nano-scaffolds. Differentiation induced by a range of agents was evaluated by immunoassays of neural protein biomarkers. PAN and PJ nanofibre scaffolds provided suitable three-dimensional (3D) environment to support the growth, differentiation and network formation of dopaminergic neuron- and astrocyte-like cell populations, respectively. The scaffolds selectively supported the survival and differentiation of both cell populations with prolonged neuronal survival when exposed to PD mimetics in the presence of astrocytes in a co-culture model. Such 3D nanoscaffold-based assays could aid our understanding of the molecular basis of PD mimetic-induced Parkinsonism and the discovery of neuroprotective agents.
目前治疗帕金森病 (PD) 的策略旨在通过恢复原始神经元结构来延缓疾病进展或替代受损神经元。神经组织再生能力差，这突出表明需要开发细胞环境来模拟 PD 的发病机制。在目前的工作中，我们已经对在聚丙烯腈 (PAN) 和 Jeffamine®掺杂聚丙烯腈 (PJ) 纳米支架上培养的人 SH-SY5Y 神经母细胞瘤和 U-87MG 神经胶质瘤细胞系的生长、存活和对 PD 模拟物的反应进行了表征。通过神经蛋白生物标志物的免疫分析评估了一系列试剂诱导的分化。PAN 和 PJ 纳米纤维支架提供了合适的三维 (3D) 环境，分别支持多巴胺能神经元样和星形胶质细胞样细胞群的生长、分化和网络形成。支架选择性地支持两种细胞群的存活和分化，在共培养模型中存在星形胶质细胞时，暴露于 PD 模拟物后神经元存活时间延长。基于 3D 纳米支架的此类测定方法可以帮助我们了解 PD 模拟物诱导的帕金森病的分子基础和神经保护剂的发现。
