Department of Biomedical Engineering, School of Engineering, Tufts University, Science & Technology Center, 4 Colby Street, Medford, MA, 02155, USA.
Initiative for Neural Science, Disease & Engineering, Tufts University, Science & Engineering Complex, 200 College Avenue, Medford, MA, 02155, USA.
Macromol Biosci. 2020 Mar;20(3):e2000004. doi: 10.1002/mabi.202000004. Epub 2020 Feb 17.
The prevalence of dementia and other neurodegenerative diseases continues to rise as age demographics in the population shift, inspiring the development of long-term tissue culture systems with which to study chronic brain disease. Here, it is investigated whether a 3D bioengineered neural tissue model derived from human induced pluripotent stem cells (hiPSCs) can remain stable and functional for multiple years in culture. Silk-based scaffolds are seeded with neurons and glial cells derived from hiPSCs supplied by human donors who are either healthy or have been diagnosed with Alzheimer's disease. Cell retention and markers of stress remain stable for over 2 years. Diseased samples display decreased spontaneous electrical activity and a subset displays sporadic-like indicators of increased pathological β-amyloid and tau markers characteristic of Alzheimer's disease with concomitant increases in oxidative stress. It can be concluded that the long-term stability of the platform is suited to study chronic brain disease including neurodegeneration.
随着人口年龄结构的变化，痴呆症和其他神经退行性疾病的患病率持续上升，这激发了人们开发长期组织培养系统来研究慢性脑部疾病。在这里，研究了一种源自人类诱导多能干细胞（hiPSC）的 3D 生物工程神经组织模型是否能够在培养中保持多年的稳定和功能。基于丝的支架被源自 hiPSC 的神经元和神经胶质细胞接种，这些 hiPSC 由健康或被诊断患有阿尔茨海默病的人类供体提供。超过 2 年，细胞保留和应激标志物仍然稳定。患病样本显示自发电活动减少，一部分样本显示出散发性的增加病理性β-淀粉样蛋白和tau 标志物的迹象，这是阿尔茨海默病的特征，同时伴有氧化应激增加。可以得出结论，该平台的长期稳定性适合研究包括神经退行性变在内的慢性脑部疾病。
