Perfused In Vitro Intestine Tissue Model to Evaluate the Role of Stromal and Immune Cells in Epithelial Response to Inflammatory Cues and Drug Therapies

ACS Appl Bio Mater. 2024 Sep 16;7(9):6078-6088. doi: 10.1021/acsabm.4c00703. Epub 2024 Aug 15.

Abstract

We establish an in vitro perfusion intestinal tissue bioreactor system tailored to study drug responses related to inflammatory bowel disease (IBD). The system includes key components including multiple human intestinal cell types (colonoids, myofibroblasts, and macrophages), a three-dimensional (3D) intestinal architecture, and fluid flow. Inclusion of myofibroblasts resulted in increased secretion of cytokines such as glypican-1 (GCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 1-α (IL-1α), whereas inclusion of macrophages resulted in increased secretion of monocyte chemoattractant proteins (MCPs) demonstrating a significant role of both stromal and immune cell types in intestinal inflammation. The system is responsive to drug treatments, as reflected in the reduction of pro-inflammatory cytokine production in tissue in some treatment scenarios. While future studies are needed to evaluate more nuanced responses in an IBD context, the present study demonstrates the ability to establish a 3D intestinal model with multiple relevant cell types and flow that is responsive to both inflammatory cues and various drug treatment options.

Keywords: colonoids; cytokine profiling; drug testing; inflammatory bowel disease; organoids; perfused bioreactor.

MeSH terms

  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Bioreactors
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / pathology
  • Intestinal Mucosa / drug effects
  • Intestines / drug effects
  • Intestines / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Materials Testing
  • Particle Size
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism

Substances

  • Biocompatible Materials
  • Cytokines