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• W4387461109 abstract "High failure rates in clinical trials for neurodegenerative disorders such as Alzheimer’s disease have been linked to an insufficient predictive validity of current animal-based disease models. This has created an increasing demand for alternative, human-based models capable of emulating key pathological phenotypes in vitro . Here, a three-dimensional Alzheimer’s disease model was developed using a compartmentalized microfluidic device that combines a self-assembled microvascular network of the human blood-brain barrier with neurospheres derived from Alzheimer’s disease-specific neural progenitor cells. To shorten microfluidic co-culture times, neurospheres were pre-differentiated for 21 days to express Alzheimer’s disease-specific pathological phenotypes prior to the introduction into the microfluidic device. In agreement with post-mortem studies and Alzheimer’s disease in vivo models, after 7 days of co-culture with pre-differentiated Alzheimer’s disease-specific neurospheres, the three-dimensional blood-brain barrier network exhibited significant changes in barrier permeability and morphology. Furthermore, vascular networks in co-culture with Alzheimer’s disease-specific microtissues displayed localized β-amyloid deposition. Thus, by interconnecting a microvascular network of the blood-brain barrier with pre-differentiated neurospheres the presented model holds immense potential for replicating key neurovascular phenotypes of neurodegenerative disorders in vitro ." @default.
• W4387461109 created "2023-10-10" @default.
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• W4387461109 date "2023-10-09" @default.
• W4387461109 modified "2023-10-11" @default.
• W4387461109 title "Accelerating the in vitro emulation of Alzheimer’s disease-associated phenotypes using a novel 3D blood-brain barrier neurosphere co-culture model" @default.
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• W4387461109 doi "https://doi.org/10.3389/fbioe.2023.1251195" @default.
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