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Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases

Author(s)
Trapecar, Martin; Wogram, Emile; Svoboda, Devon; Communal, Catherine; Omer, Attya; Lungjangwa, Tenzin; Sphabmixay, Pierre; Velazquez, Jason; Schneider, Kirsten; Wright, Charles W; Mildrum, Samuel; Hendricks, Austin; Levine, Stuart; Muffat, Julien; Lee, Meelim Jasmine; Lauffenburger, Douglas A; Trumper, David; Jaenisch, Rudolf; Griffith, Linda G; ... Show more Show less
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Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/
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Abstract
Slow progress in the fight against neurodegenerative diseases (NDs) motivates an urgent need for highly controlled in vitro systems to investigate organ-organ– and organ-immune–specific interactions relevant for disease pathophysiology. Of particular interest is the gut/microbiome-liver-brain axis for parsing out how genetic and environmental factors contribute to NDs. We have developed a mesofluidic platform technology to study gut-liver-cerebral interactions in the context of Parkinson’s disease (PD). It connects microphysiological systems (MPSs) of the primary human gut and liver with a human induced pluripotent stem cell–derived cerebral MPS in a systemically circulated common culture medium containing CD4 regulatory T and T helper 17 cells. We demonstrate this approach using a patient-derived cerebral MPS carrying the PD-causing A53T mutation, gaining two important findings: (i) that systemic interaction enhances features of in vivo–like behavior of cerebral MPSs, and (ii) that microbiome-associated short-chain fatty acids increase expression of pathology-associated pathways in PD. +
Date issued
2021
URI
https://hdl.handle.net/1721.1/136121
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)

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