Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases
Name
eabd1707.full.pdf
Description
Published version
Size
34.17 MB
Format
Adobe PDF
Checksum (MD5)
94ef5296456b1828dbdf0e70a3f4dab5
Author(s)
Trapecar, Martin
Wogram, Emile
Svoboda, Devon
Communal, Catherine
Omer, Attya
Lungjangwa, Tenzin
Sphabmixay, Pierre
Velazquez, Jason
Schneider, Kirsten
Wright, Charles W
Date Issued
2021
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Version
Final published version
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. +
MIT Department
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
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/SCIADV.ABD1707
