Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease

Ciccocioppo, Rachele; Bernardo, Maria Ester; Sgarella, Adele; Maccario, Rita; Avanzini, Maria Antonietta; Ubezio, C.; Minelli, Antonella; Alvisi, C; Vanoli, Alessandro; Calliada, Fabrizio; Dionigi, Paolo; Perotti, Cesare; Locatelli, Franco; Corazza, Gino Roberto

doi:10.1136/gut.2010.214841

Cited by 513 publications

(395 citation statements)

References 43 publications

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“…In CD, MSCs have been tested in clinical trials for two indications, namely fistulizing and luminal disease [38][39][40][41][42][43][44][45][46]. In fistulizing disease, the differentiation potential of MSCs is thought to be of crucial importance to achieve fistula tract closure.…”

Section: Msc and Ibdmentioning

confidence: 99%

Stem cell therapy for inflammatory bowel disease

2015

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Inflammatory bowel disease (IBD) could be curable by ''immune rest'' and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated ''drugstore'' is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state.Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future.

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Section: Msc and Ibdmentioning

confidence: 99%

Stem cell therapy for inflammatory bowel disease

2015

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“…3 The use of MSC as a cellular therapy is currently being explored in clinical trials, including treatment of graft-versus-host disease, 4 promotion of engraftment following hematopoietic stem cell transplantation 5 and treatment of Crohn's disease. 6 The mechanisms underlying the immune suppression by MSC are still unclear. It has been widely shown that MSC suppress the proliferation of T cells upon allogeneic or mitogenic stimulation.…”

Section: Introductionmentioning

confidence: 99%

Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6

et al. 2013

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Multipotent stromal cells have immunomodulatory capacities and have been used in transplantation and autoimmune diseases. One of the effects of multipotent stromal cells involves the inhibition of dendritic cell differentiation. Since interleukin-6 and interleukin-10 are known to play a role in inhibiting immature dendritic cell differentiation, we hypothesized that these cytokines may also mediate the inhibitory effect of human multipotent stromal cells in immature dendritic cell differentiation. In order to test this hypothesis monocytes were cultured with interleukin-4 and granulocyte-monocyte colony-stimulating factor in the presence or absence of culture-expanded bone marrow-derived multipotent stromal cells. Neutralization and cytokine-depletion strategies were applied to reveal the cellular source and effect of interleukin-6 and interleukin-10. Addition of multipotent stromal cells to monocyte cultures significantly reduced the generation of immature dendritic cells (CD14 -CD1a + ) and resulted in the generation of CD14 + CD1a -cells that displayed a significantly reduced immunostimulatory effect. We found that culture supernatants of co-cultures of multipotent stromal cells and monocytes contained higher concentrations of interleukin-6 and interleukin-10. Multipotent stromal cells produced interleukin-6 and neutralizing this interleukin-6 reversed the inhibitory effect of the multipotent cells. Interleukin-10 was not produced by multipotent stromal cells, but exclusively by monocytes after exposure to multipotent stromal cell-produced interleukin-6. In conclusion, through constitutive production of interleukin-6, multipotent stromal cells prevent the differentiation of monocytes towards antigen-presenting immunogenic cells and skew differentiation towards an antiinflammatory interleukin-10-producing cell type.Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6 Sara M. Melief, Sacha B. Geutskens, Willem E. Fibbe, and Helene Roelofs Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands ABSTRACT Introduction

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“…A summary of study characteristics is shown in Table 1, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75.…”

Section: Resultsmentioning

confidence: 99%

“…These studies assessed adipose‐derived stem cells in 143 patients. One phase I trial62 reported outcomes of mesenchymal stem cell treatment in 12 patients. Follow‐up in these studies ranged from 8 weeks to 24 months.…”

Section: Resultsmentioning

confidence: 99%

Systematic review of surgical interventions for Crohn's anal fistula

Lee

Heywood²,

Adegbola

et al. 2017

BJS Open

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BackgroundAnal fistula occurs in approximately one in three patients with Crohn's disease and is typically managed through a multimodal approach. The optimal surgical therapy is not yet clear. The aim of this systematic review was to identify and assess the literature on surgical treatments of Crohn's anal fistula.MethodsA systematic review was conducted that analysed studies relating to surgical treatment of Crohn's anal fistula published on MEDLINE, Embase and Cochrane databases between January 1995 and March 2016. Studies reporting specific outcomes of patients treated for Crohn's anal fistula were included. The primary outcome was fistula healing rate. Bias was assessed using the Cochrane ROBINS‐I and ROB tool as appropriate.ResultsA total of 1628 citations were reviewed. Sixty‐three studies comprising 1584 patients were ultimately selected in the analyses. There was extensive reporting on the use of setons, advancement flaps and fistula plugs. Randomized trials were available only for stem cells and fistula plugs. There was inconsistency in outcome measures across studies, and a high degree of bias was noted.ConclusionData describing surgical intervention for Crohn's anal fistula are heterogeneous with a high degree of bias. There is a clear need for standardization of outcomes and description of study cohorts for better understanding of treatment options.

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Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease

Abstract: Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.

Cited by 513 publications

References 43 publications

Stem cell therapy for inflammatory bowel disease

Stem cell therapy for inflammatory bowel disease

Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6

Systematic review of surgical interventions for Crohn's anal fistula

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