Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK.
Sci Rep. 2020 Apr 22;10(1):6785. doi: 10.1038/s41598-020-62906-y.
The adult human central nervous system (CNS) has very limited regenerative capability, and injury at the cellular and molecular level cannot be studied in vivo. Modelling neural damage in human systems is crucial to identifying species-specific responses to injury and potentially neurotoxic compounds leading to development of more effective neuroprotective agents. Hence we developed human neural stem cell (hNSC) 3-dimensional (3D) cultures and tested their potential for modelling neural insults, including hypoxic-ischaemic and Ca-dependent injury. Standard 3D conditions for rodent cells support neuroblastoma lines used as human CNS models, but not hNSCs, but in all cases changes in culture architecture alter gene expression. Importantly, response to damage differs in 2D and 3D cultures and this is not due to reduced drug accessibility. Together, this study highlights the impact of culture cytoarchitecture on hNSC phenotype and damage response, indicating that 3D models may be better predictors of in vivo response to damage and compound toxicity.
成人中枢神经系统（CNS）的再生能力非常有限，细胞和分子水平的损伤无法在体内进行研究。在人类系统中模拟神经损伤对于鉴定物种特异性的损伤反应和潜在的神经毒性化合物，从而开发更有效的神经保护剂至关重要。因此，我们开发了人类神经干细胞（hNSC）3 维（3D）培养物，并测试了它们用于模拟神经损伤的潜力，包括缺氧缺血和 Ca 依赖性损伤。用于作为人类中枢神经系统模型的神经母细胞瘤系的标准 3D 条件支持啮齿动物细胞，但不支持 hNSC，但是在所有情况下，培养物结构的变化都会改变基因表达。重要的是，损伤的反应在 2D 和 3D 培养物中有所不同，这并不是由于药物可及性降低所致。总之，这项研究强调了培养细胞形态对 hNSC 表型和损伤反应的影响，表明 3D 模型可能是对损伤和化合物毒性的体内反应的更好预测因子。
