Impairment of tissue resident mesenchymal stem cells in chronic ulcerative colitis and Crohn's disease.

Background and aims Little is known about the presence and function of the tissue resident mesenchymal stem cells (MtSCs) within the gastro-intestinal mucosa in health and Inflammatory Bowel Diseases (IBD). The contribution of MtSCs to the generation of inflammatory fibroblasts during IBD is also poorly understood. We hypothesized that IBD-MtSCs are impaired and contribute to the generation of the pathological myofibroblasts in IBD. Methods In a cohort of clinically and endoscopic active IBD patients and normal controls, we used quantitative RT-PCR and stem cell differentiation assays, as well confocal microscopy to characterize MtSCs. Results Expression of the stem cell markers, Oct4 and ALDH1A were increased in the inflamed IBD colonic mucosa and correlated with the increase of mesenchymal lineage marker Grem1 in ulcerative colitis (UC), but not Crohn' disease (CD). Increased proliferation and aberrant differentiation of Oct4 +Grem1 + MtSCs-like cells was observed in UC, but not in CD colonic mucosa. In contrast to normal and UC-derived MtSCs, CD-MtSCs lose their clonogenic and most of their differentiation capacities. Our data also suggests that severe damage to these cells in CD may account for the pathological PD-L1 low phenotype of CD myofibroblasts. In contrast aberrant differentiation of MtSCs appears to be involved in the appearance of pathological partially differentiated PD-L1 high myofibroblasts within the inflammed colonic mucosa in UC. Conclusion For the first time our data show that the progenitor functions of the MtSCs are differentially impaired in CD versus UC providing a scientific rationale for the use of allogeneic MSC therapy in IBD, and particularly in CD.