dc.contributor.author | Trapecar, Martin | |
dc.contributor.author | Wogram, Emile | |
dc.contributor.author | Svoboda, Devon | |
dc.contributor.author | Communal, Catherine | |
dc.contributor.author | Omer, Attya | |
dc.contributor.author | Lungjangwa, Tenzin | |
dc.contributor.author | Sphabmixay, Pierre | |
dc.contributor.author | Velazquez, Jason | |
dc.contributor.author | Schneider, Kirsten | |
dc.contributor.author | Wright, Charles W | |
dc.contributor.author | Mildrum, Samuel | |
dc.contributor.author | Hendricks, Austin | |
dc.contributor.author | Levine, Stuart | |
dc.contributor.author | Muffat, Julien | |
dc.contributor.author | Lee, Meelim Jasmine | |
dc.contributor.author | Lauffenburger, Douglas A | |
dc.contributor.author | Trumper, David | |
dc.contributor.author | Jaenisch, Rudolf | |
dc.contributor.author | Griffith, Linda G | |
dc.date.accessioned | 2021-10-27T20:30:53Z | |
dc.date.available | 2021-10-27T20:30:53Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/136121 | |
dc.description.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. + | |
dc.language.iso | en | |
dc.publisher | American Association for the Advancement of Science (AAAS) | |
dc.relation.isversionof | 10.1126/SCIADV.ABD1707 | |
dc.rights | Creative Commons Attribution NonCommercial License 4.0 | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | Science Advances | |
dc.title | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases | |
dc.type | Article | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | |
dc.contributor.department | Whitehead Institute for Biomedical Research | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Mechanical Engineering | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | |
dc.contributor.department | Massachusetts Institute of Technology. Research Laboratory of Electronics | |
dc.contributor.department | Massachusetts Institute of Technology. Center for Gynepathology Research | |
dc.relation.journal | Science Advances | |
dc.eprint.version | Final published version | |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
eprint.status | http://purl.org/eprint/status/PeerReviewed | |
dc.date.updated | 2021-07-19T16:54:30Z | |
dspace.orderedauthors | Trapecar, 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.submission | 2021-07-19T16:54:40Z | |
mit.journal.volume | 7 | |
mit.journal.issue | 5 | |
mit.license | PUBLISHER_CC | |
mit.metadata.status | Authority Work and Publication Information Needed | |