Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk.

摘要: A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, vitro technologies doing so are required human applications. prominent instance between the gut liver, whereby perturbations of one tissue can influence behavior other. Here, we present a study on gut-liver interactions under normal inflammatory contexts, via an integrative multi-organ platform comprising liver (hepatocytes Kupffer cells), intestinal (enterocytes, goblet cells, dendritic cells) models. Our results demonstrated long-term (>2 weeks) maintenance (e.g., barrier integrity) hepatic albumin) functions baseline interaction. Gene expression data comparing interaction with gut, versus isolation, revealed modulation bile acid metabolism. Intestinal FGF19 secretion associated inhibition CYP7A1 provided evidence physiologically relevant crosstalk. Moreover, significant non-linear cytokine responses was observed interaction; example, production CXCR3 ligands (CXCL9,10,11) synergistically enhanced. RNA-seq analysis upregulation IFNα/β/γ signaling during crosstalk, these pathways implicated synergistic chemokine production. Exacerbated response also negatively affected tissue-specific metabolism). These findings illustrate how integrated multi-tissue generate insights useful understanding pathophysiological processes such as organ Biotechnol. Bioeng. 2017;114: 2648-2659. © 2017 Wiley Periodicals, Inc.