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Model of the gut-liver-brain axis for studying neurodegenerative diseases

2021
Massachusetts Institute of Technology, Cambridge, USA(1)
Whitehead Institute for Biomedical Research, Cambridge, USA(2)
In the study of neurodegenerative diseases (NDs), there is 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. Here a mesofluidic platform technology to study gut-liver-cerebral interactions in the context of Parkinson’s disease (PD) was developed. 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. A patient-derived cerebral MPS carrying the PD-causing A53T mutation was used as an application example. Herein, the authors demonstrated that systemic interaction enhances features of in vivo–like behaviour of cerebral MPS, and that microbiome-associated short-chain fatty acids increase expression of pathology-associated pathways in PD.
Human physiomimetic model integrating microphysiological systems ofthe gut, liver, and brain for studies of neurodegenerative diseases
Linda G. Griffith (1), Rudolf Jaenisch(2)
#549
Added on: 05-10-2021
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