Impairment of Tissue-Resident Mesenchymal Stem Cells in Chronic Ulcerative Colitis and Crohn's Disease.
Adolescent
Adult
Aldehyde Dehydrogenase 1 Family
/ metabolism
Case-Control Studies
Cell Differentiation
Cohort Studies
Colitis, Ulcerative
/ pathology
Crohn Disease
/ pathology
Female
Humans
Intercellular Signaling Peptides and Proteins
/ metabolism
Intestinal Mucosa
/ pathology
Male
Mesenchymal Stem Cells
/ pathology
Microscopy, Confocal
Myofibroblasts
/ pathology
Octamer Transcription Factor-3
/ metabolism
Real-Time Polymerase Chain Reaction
Retinal Dehydrogenase
/ metabolism
Young Adult
Crohn’s disease
Mesenchymal stromal cells
PD-L1
inflammation
inflammatory bowel diseases
myo-/fibroblasts
stem cells
ulcerative colitis
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
02 Aug 2021
02 Aug 2021
Historique:
pubmed:
29
1
2021
medline:
16
12
2021
entrez:
28
1
2021
Statut:
ppublish
Résumé
Little 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. In 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. Expression 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. Our 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.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Little 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.
METHODS
METHODS
In 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.
RESULTS
RESULTS
Expression 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.
CONCLUSION
CONCLUSIONS
Our 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.
Identifiants
pubmed: 33506258
pii: 6121690
doi: 10.1093/ecco-jcc/jjab001
pmc: PMC8328298
doi:
Substances chimiques
GREM1 protein, human
0
Intercellular Signaling Peptides and Proteins
0
Octamer Transcription Factor-3
0
POU5F1 protein, human
0
Aldehyde Dehydrogenase 1 Family
EC 1.2.1
ALDH1A1 protein, human
EC 1.2.1.36
Retinal Dehydrogenase
EC 1.2.1.36
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1362-1375Subventions
Organisme : NCI NIH HHS
ID : R01 CA207051
Pays : United States
Organisme : NCAT
ID : TL1TR001440
Organisme : NCATS NIH HHS
ID : TL1 TR001440
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA207051
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103150
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01DK103150
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation (ECCO) 2021.
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