Adapting tissue-engineered in vitro CNS models for high-throughput study of neurodegeneration

改造组织工程体外中枢神经系统模型,用于神经退行性疾病的高通量研究

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作者:Caitriona O'Rourke, Charlotte Lee-Reeves, Rosemary Al Drake, Grant Ww Cameron, A Jane Loughlin, James B Phillips

Abstract

Neurodegenerative conditions remain difficult to treat, with the continuing failure to see therapeutic research successfully advance to clinical trials. One of the obstacles that must be overcome is to develop enhanced models of disease. Tissue engineering techniques enable us to create organised artificial central nervous system tissue that has the potential to improve the drug development process. This study presents a replicable model of neurodegenerative pathology through the use of engineered neural tissue co-cultures that can incorporate cells from various sources and allow degeneration and protection of neurons to be observed easily and measured, following exposure to neurotoxic compounds - okadaic acid and 1-methyl-4-phenylpyridinium. Furthermore, the technology has been miniaturised through development of a mould with 6 mm length that recreates the advantageous features of engineered neural tissue co-cultures at a scale suitable for commercial research and development. Integration of human-derived induced pluripotent stem cells aids more accurate modelling of human diseases, creating new possibilities for engineered neural tissue co-cultures and their use in drug screening.

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