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A Long-Living Bioengineered Neural Tissue Platform to Study Neurodegeneration.
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-02-17 , DOI: 10.1002/mabi.202000004
Nicolas Rouleau 1, 2, 3 , William L Cantley 1, 2 , Volha Liaudanskaya 1, 2 , Alexander Berk 1 , Chuang Du 1, 2 , William Rusk 1 , Emily Peirent 1 , Cole Koester 1 , Thomas J F Nieland 1, 2 , David L Kaplan 1, 2, 3
Affiliation  

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.

中文翻译:

用于研究神经退行性疾病的长寿命生物工程神经组织平台。

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,激发了用于研究慢性脑疾病的长期组织培养系统的发展。在此,我们研究了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可以在培养中保持多年稳定和功能。丝基支架上植入了来自健康或被诊断患有阿尔茨海默病的人类捐赠者提供的 hiPSC 的神经元和神经胶质细胞。细胞保留和应激标记在 2 年多的时间内保持稳定。患病样本显示出自发电活动减少,其中一部分显示出阿尔茨海默病特征性病理性 β-淀粉样蛋白和 tau 标记物增加的零星样指标,并伴有氧化应激的增加。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疾病在内的慢性脑部疾病。
更新日期:2020-02-17
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