Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip

Advanced Science
Trevor SasserathJames J Hickman

Abstract

A functional, human, multiorgan, pumpless, immune system-on-a-chip featuring recirculating THP-1 immune cells with cardiomyocytes, skeletal muscle, and liver in separate compartments in a serum-free medium is developed. This in vitro platform can emulate both a targeted immune response to tissue-specific damage, and holistic proinflammatory immune response to proinflammatory compound exposure. The targeted response features fluorescently labeled THP-1 monocytes selectively infiltrating into an amiodarone-damaged cardiac module and changes in contractile force measurements without immune-activated damage to the other organ modules. In contrast to the targeted immune response, general proinflammatory treatment of immune human-on-a-chip systems with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) causes nonselective damage to cells in all three-organ compartments. Biomarker analysis indicates upregulation of the proinflammation cytokines TNF-α, IL-6, IL-10, MIP-1, MCP-1, and RANTES in response to LPS + IFN-γ treatment indicative of the M1 macrophage phenotype, whereas amiodarone treatment only leads to an increase in the restorative cytokine IL-6 which is a marker for the M2 phenotype. This system can be used as an alternative t...Continue Reading

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Citations

Mar 16, 2021·IScience·Pamela L GraneyGordana Vunjak-Novakovic
Mar 26, 2021·Expert Opinion on Drug Metabolism & Toxicology·Jong Hwan Sung
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Mohi MiahMuzlifah Haniffa
May 14, 2021·Clinical and Translational Science·Hongbing WangShiew-Mei Huang
Sep 4, 2021·Cell·Gordana Vunjak-NovakovicMilica Radisic

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Methods Mentioned

BETA
chips
biopsies
Assay
ELISA
flow cytometry
force measurements
chip

Software Mentioned

Velocity
Autodesk Inventor
CFDAce
SigmaPlot
KC4
Clampfit
Python

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