Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases
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 f...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/136121 |
| _version_ | 1826198703968354304 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 |
| author_sort | Trapecar, Martin |
| collection | MIT |
| description | 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. + |
| first_indexed | 2024-09-23T11:08:48Z |
| format | Article |
| id | mit-1721.1/136121 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:08:48Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1361212023-12-22T20:09:03Z Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases 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 Massachusetts Institute of Technology. Department of Biological Engineering Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Research Laboratory of Electronics Massachusetts Institute of Technology. Center for Gynepathology Research 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. + 2021-10-27T20:30:53Z 2021-10-27T20:30:53Z 2021 2021-07-19T16:54:30Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136121 en 10.1126/SCIADV.ABD1707 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | 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 Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title_full | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title_fullStr | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title_full_unstemmed | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title_short | Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases |
| title_sort | human physiomimetic model integrating microphysiological systems of the gut liver and brain for studies of neurodegenerative diseases |
| url | https://hdl.handle.net/1721.1/136121 |
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