Engineering Microphysiological Immune System Responses on Chips

• Published in: Trends in biotechnology (Regular ed.) 2020-08, Vol.38 (8), p.857-872
• Main Authors: Miller, Chris P., Shin, Woojung, Ahn, Eun Hyun, Kim, Hyun Jung, Kim, Deok-Ho
• Format: Article
• Language: English
• Subjects: Antibodies; Cancer; Cell adhesion & migration; Collagen; Crosstalk; Cytotoxicity; engineering immune system responses; Gene expression; Genotype & phenotype; Human tissues; Hydrogels; Hypoxia; Immune response; Immune system; immune system-on-a-chip; Immunology; Immunotherapy; Inflammation; intestinal inflammation; Lymphocytes; Metabolism; Microfluidics; microphysiological systems; Mucosal immunity; Organs; Physiology; Proteins; systems immunology; T cell receptors; tumor immune microenvironment; Wound healing
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2020.01.003

Tissues- and organs-on-chips are microphysiological systems (MPSs) that model the architectural and functional complexity of human tissues and organs that is lacking in conventional cell monolayer cultures. While substantial progress has been made in a variety of tissues and organs, chips recapitulating immune responses have not advanced as rapidly. This review discusses recent progress in MPSs for the investigation of immune responses. To illustrate recent developments, we focus on two cases in point: immunocompetent tumor microenvironment-on-a-chip devices that incorporate stromal and immune cell components and pathomimetic modeling of human mucosal immunity and inflammatory crosstalk. More broadly, we discuss the development of systems immunology-on-a-chip devices that integrate microfluidic engineering approaches with high-throughput omics measurements and emerging immunological applications of MPSs. Human tumor immune microenvironment-on-a-chip models have been developed to emulate cell-type-dependent interactions, physical and chemical perturbations, and the infiltration and cytotoxicity of therapeutic antitumor lymphocytes and clinically relevant immunomodulatory agents.Intestinal inflammation-on-a-chip models recapitulating the 3D intestinal transmural interface have been developed to discover how pathophysiological factors impair the intercellular crosstalk in the epithelium-microbiome-immune axis and trigger chronic inflammatory immune responses.Combining engineered microphysiological immune system responses with high-throughput multiomics measurements at the single-cell level facilitates a systems immunology-on-a-chip approach to gain novel insights into immune disorders.Immune cells are being incorporated in tissues- and organs-on-chips modeling a variety of diseases.