Impairment of Tissue-Resident Mesenchymal Stem Cells in Chronic Ulcerative Colitis and Crohn’s Disease

Abstract

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.

The Therapeutic Efficacy of Adipose Tissue-Derived Mesenchymal Stem Cell Conditioned Medium on Experimental Colitis Was Improved by the Serum From Colitis Rats

“…These results indicated that the cells we obtained meet the minimum markers to confirm the MSCs. Previous investigations have found that MSCs or the exosome secreted from MSCs could significantly alleviate ulcerative colitis (Yang et al, 2020;Grim et al, 2021). Consistent with these results, our study showed the conditioned media from MSC significantly attenuated inflammatory responses and improve the colitis.…”

“…MSCs are multipotent cells which have been tested in clinical studies for the treatment of IBD. In recent years, MSCs have garnered substantial interest because they have low immunogenicity and are easy to be extracted from adult adipose and bone marrow tissues (Grim et al, 2021). One of the important features of MSCs is the capacity of tri-lineage differentiation, and our result in Figure 1C showed that the cells we obtained had the potentials to differentiate into osteocytes, adipocytes and chondrocytes.…”

Wogonin Strengthens the Therapeutic Effects of Mesenchymal Stem Cells in DSS‐Induced Colitis via Promoting IL‐10 Production

“…The cells sprinted into the clinic stage center due to their features of versatile development potential, self-renewal, allogenic compatibility, and immunomodulatory effects. MSCs are currently being widely tested as a cellular therapy in chronic intestinal diseases, including IBD, and showed promising clinical outcomes with unmet optimization and improvement [28][29][30], such as in vivo low level of MSC recruitment, and persistence decreased their therapeutic efficacy [31].…”

New perspectives on treatment of gastrointestinal diseases: therapeutic potential of mesenchymal stromal cells

“…Cell therapy for inflammatory bowel diseases seems to be all the more reasonable since these diseases are accompanied by dysfunctions of resident MSCs which are important components of the microenvironment of the intestinal epithelium. Thus, increased proliferative activity of MSCs of the colon mucosa was found in patients with ulcerative colitis, and in patients with Crohn's disease, a loss of the ability of these cells to clonal growth was reported; in both cases, differentiation potentials of MSCs were altered (Grim et al, 2021). There is a fairly large experience of clinical use of MSCs in complex therapy in patients with Crohn's disease and ulcerative colitis.…”