scholarly journals Gut Mesenchymal Stromal Cells in Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Valeria Messina ◽  
Carla Buccione ◽  
Giulia Marotta ◽  
Giovanna Ziccheddu ◽  
Michele Signore ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Class Ii ◽  
Immune Modulator ◽  
Hla Dr ◽  
Class Ii Mhc ◽  
Intestinal Submucosa ◽  
Antigen Presenting

Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal). In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC). The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ) is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

scholarly journals Immunomodulatory Effects of Mesenchymal Stromal Cells in Crohn’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ilse Molendijk ◽  
Marjolijn Duijvestein ◽  
Andrea E. van der Meulen-de Jong ◽  
Welmoed K. van Deen ◽  
Marloes Swets ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Perianal Fistulas ◽  
Allogeneic Mscs ◽  
New Treatment ◽  
Oxide Synthase ◽  
Phase I And Ii

The ability of mesenchymal stromal cells (MSCs) to suppress immune responses combined with their potential to actively participate in tissue repair provides a strong rationale for the use of MSCs as a new treatment option in diseases characterized by inflammation and severe tissue damage, such as Crohn’s disease (CD) and perianal fistulas. Multiple studies have shown that MSCs suppress a range of immune cells, such as dendritic cells (DC), naïve and effector T cells, and natural killer (NK) cells. Recently published papers attribute the immunosuppressive capacity of MSCs to soluble factors produced by MSCs, such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO). Promising results are obtained from phase I and II clinical trials with autologous and allogeneic MSCs as treatment for refractory CD and perianal fistulas; however the question remains: what are the molecular mechanisms underlying the immunomodulating properties of MSCs? This paper highlights the present knowledge on the immunosuppressive effects of MSCs and its complexity in relation to CD and perianal fistulas.

scholarly journals Allogeneic Bone Marrow–Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn’s Disease

2015 ◽  
Vol 149 (4) ◽  
pp. 918-927.e6 ◽  
Author(s):  
Ilse Molendijk ◽  
Bert A. Bonsing ◽  
Helene Roelofs ◽  
Koen C.M.J. Peeters ◽  
Martin N.J.M. Wasser ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Perianal Fistulas

scholarly journals HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 395-401 ◽  
Author(s):  
P C F Stokkers ◽  
P H Reitsma ◽  
G N J Tytgat ◽  
S J H van Deventer
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Meta Analysis ◽  
Class Ii ◽  
Hla Class Ii ◽  
Negative Association ◽  
Hla Dr ◽  
Inflammatory Bowel

BACKGROUNDSusceptibility to inflammatory bowel disease (IBD) is partially genetically determined and the HLA class II genes are candidates for a role in genetic susceptibility to IBD, because their products play a central role in the immune response. Multiple studies have reported associations between HLA-DR or -DQ phenotypes and either ulcerative colitis or Crohn’s disease, but much of the data are still controversial.AIMSTo estimate overall associations between HLA class II phenotypes and IBD, and to establish the relative risk conferred by HLA-DR and -DQ phenotypes by meta-analysis.METHODSMedline was searched for publications reporting on the relation between IBD and HLA class II phenotypes. Raw data were extracted by recalculating the number of phenotypes or the number of alleles of the main antigens. Odds ratios and confidence intervals were calculated according to the Mantel-Haenszel method.RESULTSDR2, DR9, and DRB1*0103 were positively associated with ulcerative colitis, and a negative association was found for DR4 and ulcerative colitis. For Crohn’s disease a positive association was found with DR7, DRB3*0301, and DQ4 and a negative association with DR2 and DR3.CONCLUSIONSBoth ulcerative colitis and Crohn’s disease are associated with specific HLA class II phenotypes. Further analysis of these phenotypes and subgroup analysis may elucidate how these alleles contribute to susceptibility to IBD.

OC.07.3 IN VITRO EFFECTS OF MESENCHYMAL STROMAL CELLS (MSC) ON T CELL LINES FROM CROHN'S DISEASE PATIENTS

2013 ◽  
Vol 45 ◽  
pp. S71
Author(s):  
R. Ciccocioppo ◽  
G.C. Cangemi ◽  
E. Betti ◽  
A. Gallia ◽  
V. Imbesi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Cell Lines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
In Vitro Effects ◽  
T Cell Lines

Allogeneic mesenchymal stromal cells for refractory luminal Crohn’s disease: A phase I–II study

2018 ◽  
Vol 50 (11) ◽  
pp. 1251-1255 ◽  
Author(s):  
Céline Gregoire ◽  
Alexandra Briquet ◽  
Caroline Pirenne ◽  
Chantal Lechanteur ◽  
Edouard Louis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase I ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

scholarly journals Tu1227 Treatment of Refractory Crohn's Disease With Allogeneic, Bone Marrow-Derived Adult Mesenchymal Stromal Cells

2012 ◽  
Vol 142 (5) ◽  
pp. S-779
Author(s):  
Renate Schmelz ◽  
Stefan Brueckner ◽  
Jana Babatz ◽  
Katja Richter ◽  
Nadine Muench ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone

Phenotypical/functional characterization of in vitro-expanded mesenchymal stromal cells from patients with Crohn's disease

Cytotherapy ◽  
2009 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Maria Antonia Avanzini ◽  
Rachele Ciccocioppo ◽  
Cesare Perotti ◽  
Angela Maria Cometa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Functional Characterization

scholarly journals The role of mesenchymal stromal cells in the treatment of ulcerative colitis and Crohn's disease

2016 ◽  
pp. 730-753
Author(s):  
Céline Gregoire ◽  
Chantal Lechanteur ◽  
Alexandra Briquet ◽  
Etienne Baudoux ◽  
Olivier Giet ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

scholarly journals Crohn’s Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat

2021 ◽  
Vol 22 (8) ◽  
pp. 4292
Author(s):  
Ana Madeira ◽  
Carolina Serena ◽  
Miriam Ejarque ◽  
Elsa Maymó-Masip ◽  
Monica Millan ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Wilms Tumor ◽  
Expression Profiles ◽  
Subcutaneous Fat ◽  
Hla Dr ◽  
Wide Range ◽  
Antigen Presenting

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn’s disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn’s disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms’ tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn’s disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen—DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn’s disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn’s disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn’s disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

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