IBD-Derived Colonic Fibroblasts Exhibit an Osteopontin-Enriched Secretome, and Osteopontin Restrains Human Colonic Organoid Maturation
Background: Intestinal fibroblasts are extensively remodeled in inflammatory bowel disease (IBD), yet the soluble stromal signals that directly influence epithelial maturation remain incompletely understood. We examined whether fibroblasts derived from inflamed IBD colon display an osteopontin (OPN; SPP1)-enriched secretory phenotype and whether extracellular OPN directly modifies non-neoplastic…
Inflammatory bowel disease (IBD) causes significant remodeling of intestinal fibroblasts, but the specific soluble stromal signals that impact epithelial maturation are not fully understood. A study has now investigated whether fibroblasts derived from inflamed IBD colon exhibit an osteopontin (OPN)-enriched secretory phenotype and if extracellular OPN can modify non-neoplastic human colonic epithelium.
The researchers collected conditioned media from both noninflamed-associated fibroblast (NAF) and inflammatory-associated fibroblast (IAF) cultures, which were then analyzed using a multi-donor cytokine-array matrix. The data revealed a strong positive correlation between OPN levels in IAF and NAF cultures, with IAF cells displaying approximately 10 times higher mean SPP1 expression compared to NAF cells (P = 0.0159).
To further validate these findings, the team employed recombinant OPN in human colonic organoids obtained from three donors. Donor identity was used to define biological replication.
The study concluded that OPN is enriched in the secretome of IBD-derived colonic fibroblasts, and this osteopontin-enriched environment restrains human colonic organoid maturation.
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