背景(考古学)
诱导多能干细胞
微生物群
免疫系统
神经科学
肠道微生物群
生物
疾病
免疫学
生物信息学
医学
病理
基因
遗传学
胚胎干细胞
古生物学
作者
Martin Trapečar,Emile Wogram,Devon S. Svoboda,Catherine Communal,Attya Omer,Tenzin Lungjangwa,Pierre Sphabmixay,Jason Velazquez,Katrin Schneider,C. Wayne Wright,Samuel Mildrum,Austin Hendricks,Seymour Levine,Julien Muffat,Meelim Jasmine Lee,Douglas A. Lauffenburger,David L. Trumper,Rudolf Jaenisch,Linda G. Griffith
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-01-29
卷期号:7 (5)
被引量:73
标识
DOI:10.1126/sciadv.abd1707
摘要
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.
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