Impairment of Tissue-Resident Mesenchymal Stem Cells in Chronic Ulcerative Colitis and Crohn’s Disease
| Autor: | Yuriy Fofanov, Paul Johnson, Tammara L Watts, Don W. Powell, Walter A. Koltun, Gabriela Uribe, Kamil Khanipov, Carl Grim, Gregory S Yochum, Irina V. Pinchuk, Ellen J Beswick, Robert Noble |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Adolescent Cellular differentiation Inflammation Real-Time Polymerase Chain Reaction Stem cell marker Inflammatory bowel disease Aldehyde Dehydrogenase 1 Family Cohort Studies Young Adult Crohn Disease medicine Humans Intestinal Mucosa Myofibroblasts Crohn's disease Microscopy Confocal business.industry Mesenchymal stem cell Gastroenterology Retinal Dehydrogenase Cell Differentiation Mesenchymal Stem Cells Original Articles General Medicine medicine.disease Ulcerative colitis digestive system diseases Case-Control Studies Cancer research Intercellular Signaling Peptides and Proteins Colitis Ulcerative Female medicine.symptom Stem cell business Octamer Transcription Factor-3 |
| Zdroj: | J Crohns Colitis |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjab001 |
| Popis: | Background and AimsLittle is known about the presence and function of tissue-resident mesenchymal stem cells [MtSCs] within the gastrointestinal mucosa in health and inflammatory bowel disease [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.MethodsIn a cohort of clinically and endoscopically active IBD patients and normal controls, we used quantitative RT-PCR and stem cell differentiation assays, as well as confocal microscopy, to characterize MtSCs.ResultsExpression of two stem cell markers, Oct4 and ALDH1A, was increased in the inflamed IBD colonic mucosa and correlated with an increase of the mesenchymal lineage marker Grem1 in ulcerative colitis [UC], but not Crohn’s disease [CD]. Increased proliferation and aberrant differentiation of Oct4+Grem1+ MtSC-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 suggest that severe damage to these cells in CD may account for the pathological PD-L1low phenotype of CD myofibroblasts. In contrast, aberrant differentiation of MtSCs appears to be involved in the appearance of pathological partially differentiated PD-L1high myofibroblasts within the inflammed colonic mucosa in UC.ConclusionOur data show, for the first time, that the progenitor functions of MtSCs are differentially impaired in CD vs UC, providing a scientific rationale for the use of allogeneic MSC therapy in IBD, and particularly in CD. |
| Databáze: | OpenAIRE |
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