A model for Crohn’s disease post-ileal resection fibrosis development using human ileal enteroids and myofibroblasts

Background: Fibrosis and inflammation frequently emerge soon after ileal resection for strictures in Crohn's disease (CD). Objective: This study examined the profibrotic and proinflammatory effects of conditioned media from TNF and IFN-γ (T+I)-exposed healthy and inactive CD ileal enteroids (CDiE) on subepithelial myofibroblasts (SEMF), modeling early post-ileal resection conditions in CD. Methods: Ileal enteroids from healthy subjects (HE) and inactive CD patients (CDiE) were exposed to T+I for 6 hours, followed by an 18-hour conditioning period. Conditioned media were collected and applied to human intestinal myofibroblasts (HIMF) from healthy and inactive CD ileum for 24 hours to assess proinflammatory and profibrotic gene expression. Results: ). Conclusion: . This model of the early post-ileal resection state provides a platform to identify key targets for preventing fibrosis progression and potentially reducing the need for repeat ileal surgery in CD patients.