Accelerating the in vitro emulation of Alzheimer's disease-associated phenotypes using a novel 3D blood-brain barrier neurosphere co-culture model.

Autor:	Ko EC; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States., Spitz S; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States., Pramotton FM; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States., Barr OM; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Xu C; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Pavlou G; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States., Zhang S; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States., Tsai A; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Maaser-Hecker A; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Jorfi M; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Choi SH; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Tanzi RE; Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States., Kamm RD; Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2023 Oct 09; Vol. 11, pp. 1251195. Date of Electronic Publication: 2023 Oct 09 (Print Publication: 2023).
DOI:	10.3389/fbioe.2023.1251195
Abstrakt:	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 . Competing Interests: RK is a co-founder of AIM Biotech, a company that markets microfluidic technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ko, Spitz, Pramotton, Barr, Xu, Pavlou, Zhang, Tsai, Maaser-Hecker, Jorfi, Choi, Tanzi and Kamm.)
Databáze:	MEDLINE
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