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
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