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dc.contributor.authorTrapecar, Martin
dc.contributor.authorWogram, Emile
dc.contributor.authorSvoboda, Devon
dc.contributor.authorCommunal, Catherine
dc.contributor.authorOmer, Attya
dc.contributor.authorLungjangwa, Tenzin
dc.contributor.authorSphabmixay, Pierre
dc.contributor.authorVelazquez, Jason
dc.contributor.authorSchneider, Kirsten
dc.contributor.authorWright, Charles W
dc.contributor.authorMildrum, Samuel
dc.contributor.authorHendricks, Austin
dc.contributor.authorLevine, Stuart
dc.contributor.authorMuffat, Julien
dc.contributor.authorLee, Meelim Jasmine
dc.contributor.authorLauffenburger, Douglas A
dc.contributor.authorTrumper, David
dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorGriffith, Linda G
dc.date.accessioned2021-10-27T20:30:53Z
dc.date.available2021-10-27T20:30:53Z
dc.date.issued2021
dc.identifier.urihttps://hdl.handle.net/1721.1/136121
dc.description.abstractSlow 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. +
dc.language.isoen
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.relation.isversionof10.1126/SCIADV.ABD1707
dc.rightsCreative Commons Attribution NonCommercial License 4.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScience Advances
dc.titleHuman physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases
dc.typeArticle
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.departmentWhitehead Institute for Biomedical Research
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineering
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology
dc.contributor.departmentMassachusetts Institute of Technology. Research Laboratory of Electronics
dc.contributor.departmentMassachusetts Institute of Technology. Center for Gynepathology Research
dc.relation.journalScience Advances
dc.eprint.versionFinal published version
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2021-07-19T16:54:30Z
dspace.orderedauthorsTrapecar, M; Wogram, E; Svoboda, D; Communal, C; Omer, A; Lungjangwa, T; Sphabmixay, P; Velazquez, J; Schneider, K; Wright, CW; Mildrum, S; Hendricks, A; Levine, S; Muffat, J; Lee, MJ; Lauffenburger, DA; Trumper, D; Jaenisch, R; Griffith, LG
dspace.date.submission2021-07-19T16:54:40Z
mit.journal.volume7
mit.journal.issue5
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Needed


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