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 ◽  
...  

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.

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 ◽  
...  

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S346-S347
Author(s):  
O Knyazev ◽  
A V Kagramanova ◽  
A Lishchinskaya ◽  
T Shkurko ◽  
I Li ◽  
...  

Abstract Background Perianal fistulas are common types of fistulas in Crohn’s disease (CD). Mesenchymal stromal cells (MSC), which have immunomodulatory properties and high regenerative potential, are currently also used for the treatment of fistula CD. The purpose of this study was to compare the effectiveness of combined therapy (local and systemic) mesenchymal stromal cells (MSC) of bone marrow, in the effectiveness of combination therapy MSC (local administration) and infliximab (IFX), as therapy the IFX with immunomodulators on the healing of simple perianal fistulas in Crohn’s disease (CD). Methods Seventy-five patients with CD with perianal lesions were divided into three groups depending on the method of therapy. The first group of СD patients aged 19 to 59 years (Me-29) (n=25) received a culture of MSC systematically according to the scheme and locally. The second group of patients with CD (n=25) aged 20 to 60 years (Me-28) received anti-cytokine therapy with IFX and immunomodulators. The third group of patients with CD (n=25) aged 20 to 62 years (Me-30) received MSC systemically and locally, as well as anti-cytokine therapy with IFX. The dynamics evaluated the complete closure of the external opening of the fistula. Ano-and rectosigmoscopy was performed 2 and 12 months after the start of therapy. The comparative analysis was performed using four-field tables using nonparametric statistical criteria. Results After 2 months in the first group of patients, healing of simple fistulas was observed in 15/25 (60.0%), in the third group-22/25 patients (88.0%) (RR–1.467; 95% CI - 1.032-2.084; x2= 3.742; p=0.02948). After 2 months in the second group, healing of simple fistulas was observed in 16/25 (64.0%) (RR-1.37; 95% CI 0.991-1.908; x2=4.091; p=0.056). After 12 months in the first group of patients, healing of simple fistulas was observed in 17/25 (68.0%), in the third group-24/25 (96.0%) patients (RR 1.412; 95% CI 1.066–1.869; x2=7.399; p=0.0124). After 12 months in the second group, healing of simple fistulas occurred in 18/25 (72.0%) (RR -0.750; 95% CI 0.580– 0.970; x2=5.922; p=0.0488). Conclusion Combined cells and anti-cytokine therapy of CD with perianal lesions contributes to more frequent and prolonged closure of simple fistulas, compared with MSC monotherapy and IFX monotherapy.


Immunotherapy ◽  
2018 ◽  
Vol 10 (14) ◽  
pp. 1203-1217 ◽  
Author(s):  
Jesús Castro-Poceiro ◽  
Agnès Fernández-Clotet ◽  
Julián Panés

2013 ◽  
Vol 45 ◽  
pp. S71
Author(s):  
R. Ciccocioppo ◽  
G.C. Cangemi ◽  
E. Betti ◽  
A. Gallia ◽  
V. Imbesi ◽  
...  

2018 ◽  
Vol 50 (11) ◽  
pp. 1251-1255 ◽  
Author(s):  
Céline Gregoire ◽  
Alexandra Briquet ◽  
Caroline Pirenne ◽  
Chantal Lechanteur ◽  
Edouard Louis ◽  
...  

2012 ◽  
Vol 142 (5) ◽  
pp. S-779
Author(s):  
Renate Schmelz ◽  
Stefan Brueckner ◽  
Jana Babatz ◽  
Katja Richter ◽  
Nadine Muench ◽  
...  

Cytotherapy ◽  
2009 ◽  
pp. 1-12 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Maria Antonia Avanzini ◽  
Rachele Ciccocioppo ◽  
Cesare Perotti ◽  
Angela Maria Cometa ◽  
...  

Author(s):  
Céline Gregoire ◽  
Chantal Lechanteur ◽  
Alexandra Briquet ◽  
Etienne Baudoux ◽  
Olivier Giet ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Valeria Messina ◽  
Carla Buccione ◽  
Giulia Marotta ◽  
Giovanna Ziccheddu ◽  
Michele Signore ◽  
...  

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.


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