@article{4756,
  keywords = {Alzheimer's disease (AD), blood-brain barrier (BBB), microfluidics, microphysiological system (MPS), neurospheres},
  author = {Eunkyung Clare Ko and Sarah Spitz and Francesca Michela Pramotton and Olivia M. Barr and Ciana Xu and Georgios Pavlou and Shun Zhang and Alice Tsai and Anna Maaser-Hecker and Mehdi Jorfi and Se Hoon Choi and Rudolph E. Tanzi and Roger D. Kamm},
  title = {Accelerating the in vitro emulation of Alzheimer’s disease-associated phenotypes using a novel 3D blood-brain barrier neurosphere co-culture model},
  abstract = {<p>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 <italic>in vitro</italic>. 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 <italic>in vivo</italic> 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 <italic>in vitro</italic>.</p>},
  year = {2023},
  journal = {Frontiers in Bioengineering and Biotechnology},
  volume = {11},
  month = {2023-10-09},
  issn = {2296-4185},
  url = {https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1251195/full},
  doi = {10.3389/fbioe.2023.1251195},
  language = {English},
}