Stem cell-based therapies in inflammatory bowel disease: promises and pitfalls

Duran, Natalie E.; Hommes, Daniël W.

doi:10.1177/1756283x16642190

Cited by 37 publications

(23 citation statements)

References 116 publications

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“…However, staining for α-SMA, a marker of differentiated MSC, demonstrated that, at least in UC, the majority of PD-L1 expressing cells were identified as myofibroblasts. Further, the reduction of PD-L1 in CD may serve as a scientific rationale for the use of “PD-L1 competent” MSCs for the treatment of perianal CD where the major objective is to deposit these stem cells locally in fistulizing tracts to suppress the local inflammatory responses ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Beswick¹,

Grim

Singh

et al. 2018

Front. Immunol.

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Background and AimsThe role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses.MethodsTissues and cells derived from Crohn’s disease (CD), ulcerative colitis (UC), and healthy individuals (N) were studied in situ, ex vivo, and in culture.ResultsA significant increase in programmed death-ligand 1 (PD-L1) was observed in the inflamed UC colonic mucosa when compared to the non-inflamed matched tissue samples, CD, and healthy controls. UC-CMFs were among the major populations in the colonic mucosa contributing to the enhanced PD-L1 expression. In contrast, PD-L1 expression was decreased in CD-CMFs. When compared to CD-CMFs and N-CMFs, UC-CMFs demonstrated stronger suppression of IL-2, Th1 transcriptional factor Tbet, and IFN-γ expression by CD3/CD28-activated CD4+ T cells, and this process was PD-L1 dependent. Similar observations were made when differentiated Th1 cells were cocultured with UC-CMFs. In contrast, CD-CMFs showed reduced capacity to suppress Th1 cell activity and addition of recombinant PD-L1 Fc to CD-CMF:T cell cocultures partially restored the suppression of the Th1 type responses.ConclusionWe present evidence showing that increased PD-L1 expression suppresses Th1 cell activity in UC. In contrast, loss of PD-L1 expression observed in CD contributes to the persistence of the Th1 inflammatory milieu in CD. Our data suggest that dysregulation of the Th1 responses in the inflamed colonic mucosa of IBD patients is promoted by the alterations in PD-L1 expression in the mucosal mesenchymal stromal cell compartment.

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Section: Discussionmentioning

confidence: 99%

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Beswick¹,

Grim

Singh

et al. 2018

Front. Immunol.

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“…Transplant data from 2013 show that over 320,000 patients have received either autologous or allogeneic stem-cell transplants for various indications. 14,15 There are only a few studies reporting mesenchymal stem cell transplantation (MSCT) in IBD patients, especially in UC and several publications about MSCT in patients with pyoderma gangrenosum, but not in combination ogf these diseases. [16][17][18] In this clinical case we tried to analyze some peculiarities of clinical course in patient with UC and PG the consequences of standard treatment algorithm and MSCT applied for this patient.…”

Section: Discussionmentioning

confidence: 99%

Mesenhymal stem cells in treatment of pyoderma gangrenosum in patient with ulcerative colitis: clinical case

Dorofeyev¹,

Попандопуло²,

Dorofeyeva³

et al. 2019

GHOA

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Keywords: severe ulcerative colitis, pyoderma gangrenosum, mesenhymal stem cells transplantation clinical case Gastroenterology & Hepatology: Open Access Case Report Open Access Mesenhymal stem cells in treatment of pyoderma gangrenosum in patient with ulcerative colitis: clinical case 57 Copyright: ©2019 Dorofeyev et al. Citation: Dorofeyev AE, Popandopulo AG, Dorofeyeva AA, et al. Mesenhymal stem cells in treatment of pyoderma gangrenosum in patient with ulcerative colitis: clinical case.

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“…Transplantation of HSCs and MSCs have shown beneficial effects in treating certain types of CD in clinical trials (Forbes et al, ; Hawkey, ; Panés et al, ), although they are believed to mainly possess immunomodulatory actions (Duran & Hommes, ; Okamoto & Watanabe, ). Nonetheless, MSCs appear indirectly to be able to promote epithelial repair by contributing to the ISCs' niche and by regulating claudin expression in TJs (Tanaka et al, ; Yabana et al, ).…”

Section: Re‐establishing Epithelial Barrier Integrity By Means Of Stementioning

confidence: 99%

Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

Holmberg

Pedersen

Jørgensen

et al. 2017

J Tissue Eng Regen Med

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Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, which includes increased epithelial cell death, modified mucus configuration, altered expression and distribution of tight junction proteins, along with a decreased expression of antimicrobial peptides. Inflammatory bowel disease is associated with life-long morbidity for affected patients, and both the incidence and prevalence is increasing globally, resulting in substantial economic strain for society. Mucosal healing and re-establishment of barrier integrity are associated with clinical remission, as well as with an improved patient outcome. Hence, these factors are vital treatment goals, which conventionally are achieved by a range of medical treatments, although none are effective in all patients, resulting in several patients still requiring surgery at some point. Therefore, novel treatment strategies to accomplish mucosal healing and to re-establish normal barrier integrity in inflammatory bowel disease are warranted, and luminal stem cell-based approaches might have an intriguing potential. Transplantation of in vitro expanded intestinal epithelial stem cells derived either directly from mucosal biopsies or from directed differentiation of human pluripotent stem cells may constitute complementary treatment options for patients with mucosal damage, as intestinal epithelial stem cells are multipotent and may give rise to all epithelial cell types of the intestine. This review provides the reader with a comprehensive state-of-the-art overview of the intestinal barrier's role in healthy and diseased states, discussing the clinical application of stem cell-based approaches to accomplish mucosal healing in inflammatory bowel disease.

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Stem cell-based therapies in inflammatory bowel disease: promises and pitfalls

Cited by 37 publications

References 116 publications

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Mesenhymal stem cells in treatment of pyoderma gangrenosum in patient with ulcerative colitis: clinical case

Intestinal barrier integrity and inflammatory bowel disease: Stem cell‐based approaches to regenerate the barrier

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