Patient-derived tissue slice cultures from endoscopic biopsies as a translational ex vivo model for inflammatory...

Effective inflammatory bowel disease (IBD) management increasingly relies on patient-stratified therapeutic approaches, yet clinically accessible platforms for ex vivo pharmacological evaluation remain limited. This study establishes patient-derived tissue slice cultures from routine endoscopic biopsies (ePDTC), as a potential translational platform for individualized drug response assessment. ePDTC were generated from routine colonic biopsies of ulcerative colitis (UC, N = 11), Crohn's disease (CD, N = 7), and non-IBD control patients (N = 3). Tissue slices (350 μm high) were cultured at an air-liquid interface for 24 and 48 h, assessed for viability, immune cell composition, transcription factor activation, and mediator release profiles. Pharmacological responsiveness was evaluated using budesonide (1 µM) and myrrh extracts (50-100 µg/mL). Structural integrity was preserved in 88.4% of ePDTC at 24 h after start of cultivation with low apoptosis rates (median: 1.21%), but declined to 56.0% of tissues at 48 h. ePDTC preserved disease-specific inflammatory signatures, including distinct neutrophil patterns between UC and CD subtypes. Budesonide significantly reduced 17 of 24 inflammatory mediators after 24 h (adjusted P < 0.001) with indication of disease subtype-specific response patterns in principal component analysis. Myrrh extracts demonstrated concentration-dependent responses. Biopsy-derived ePDTC provide a clinically accessible ex vivo platform that preserves native tissue complexity and demonstrates the capacity to capture inter-individual pharmacodynamic heterogeneity within a 24-hour experimental window. This provides a biological basis for future patient-stratified pharmacological evaluation.