Cytokine induced inflammatory bowel disease model using organ-on-a-chip technology

PLoS One. 2023 Dec 13;18(12):e0289314. doi: 10.1371/journal.pone.0289314. eCollection 2023.

Abstract

Over 2 million people in North America suffer from inflammatory bowel disease (IBD), a chronic and idiopathic inflammatory condition. While previous research has primarily focused on studying immune cells as a cause and therapeutic target for IBD, recent findings suggest that non-immune cells may also play a crucial role in mediating cytokine and chemokine signaling, and therefore IBD symptoms. In this study, we developed an organ-on-a-chip co-culture model of Caco2 epithelial and HUVEC endothelial cells and induced inflammation using pro-inflammatory cytokines TNF-α and IFN-γ. We tested different concentration ranges and delivery orientations (apical vs. basal) to develop a consistently inducible inflammatory response model. We then measured pro-inflammatory cytokines and chemokines IL-6, IL-8, and CXCL-10, as well as epithelial barrier integrity. Our results indicate that this model 1. induces IBD-like cytokine secretion in non-immune cells and 2. decreases barrier integrity, making it a feasible and reliable model to test the direct actions of potential anti-inflammatory therapeutics on epithelial and endothelial cells.

MeSH terms

  • Caco-2 Cells
  • Cytokines*
  • Endothelial Cells
  • Humans
  • Inflammatory Bowel Diseases*
  • Intestinal Mucosa
  • Microphysiological Systems

Substances

  • Cytokines

Grants and funding

Oregon State University College of Science SCiRisIII funding: https://internal.science.oregonstate.edu/rdu/internal-research-funding-program, Oregon State University Microbiology Department New Professor Start-up funding, Oregon State University Research Equipment Reserve Fund, Larry W. Martin & Joyce B. O’Neill Endowed Fellowship The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.