Review article: In vitro models in inflammatory bowel disease research—a critical review

Abstract

SUMMARY Research efforts in inflammatory bowel disease (IBD) have been directed towards the epithelium as it has become clear that epithelial cells play a critical role in inflammatory response. Most research involving IBD employs in vitro techniques. In vitro epithelial cell studies have played and are continuing to play a major role in providing specific information relevant to IBD. Thus, such studies have provided irrefutable evidence that epithelial responses can be induced by microbes/microbial products and by immune activation. Culture experiments have provided insights into the effects of individual cytokines and other inflammatory mediators on epithelial pathophysiology, injury and repair, apoptosis, necrosis, and other processes that may be involved in IBD. Activated epithelial cells can participate in and even orchestrate immune responses, by stimulating T cells (and possibly others) and by producing cytokines that recruit specific inflammatory cells. Physiological regulation of epithelial tight junctions has been demonstrated by in vitro studies; the implication of this information for treating IBD is just beginning to be explored. It is becoming increasingly clear that epithelial processing and presentation of antigens is critical to the outcome of the immune response.

Discovering probiotic microorganisms: in vitro, in vivo, genetic and omics approaches

“…In vitro models for probiotic selection in IBD research are alike to those mentioned previously. Specifically, assays that investigate the antimicrobial activity against microbes that help alter microbial biodiversity within the gut, the regulation of epithelial tight junctions and the induction of an anti-inflammatory cytokine profile (high IL-10/IL-12 ratio) from immune cells, are commonly used ( McKay et al, 1997 ; Foligne et al, 2007 ).…”

Exploring and Enhancing the Anti‐Inflammatory Properties of Polymeric Formula

“…Certainly, HT‐29 cells are tumor cells derived from human colonic adenocarcinoma; as such, these cell lines have unique properties different from that of normal intestinal cells (eg, genetic makeup, metabolic profile, and other cellular physiological properties) 49 . The cell culture conditions in which these cells are maintained also do not typically represent the local environment in situ 50 . Moreover, what happens to PF when it passes through the stomach and small intestine before being delivered to the colon has not been investigated.…”

Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems

“…Several genes have been identified including those involved in innate immune signaling pathways (ITLN1) (71), autophagy (IRGM) (72), ER stress responses (ORMDL3) (73), and negative regulators of interferon-gamma (INF-γ) signaling (PTPN2) (74). The cornerstone therapies for IBD are immunosuppressive drugs and steroids, both of which provide variable benefit to the IBD population (75). …”

“…Immune and epithelial cells release a variety of signaling factors and peptides to regulate the inflammatory response (cytokines), recruit phagocytes (chemokines) and facilitate epithelial repair (growth factors) (75) (Figure 7). To better understand these key components in IBD, in vitro models have focused on a variety of culture systems utilizing one or more cell types.…”

“…This approach has been particularly effective for studies exploring perturbations in epithelial permeability (i.e. transepithelial electrical resistance) brought out by inflammatory responses (75, 87, 88). …”