A Phase 2 Study of Allogeneic Mesenchymal Stromal Cells for Luminal Crohn's Disease Refractory to Biologic Therapy

Forbes, Geoffrey M; Sturm, M.; Leong, Rupert W.; Sparrow, Miles P.; Segarajasingam, Dev S.; Cummins, Adrian G.; Phillips, Michael; Herrmann, Richard

doi:10.1016/j.cgh.2013.06.021

Cited by 289 publications

(213 citation statements)

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“…gov/ct2/show/NCT01090817). Twelve patients out of 14 were improved, including eight patients with remission and seven patients of the endoscopic improvement [47]. These studies were not designed to assess efficacy, but did demonstrate the prospective efficacy and safety of intravenous (i.v.)…”

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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“…A number of trials indicate that stem cells hold great promise for cell-based therapy in general. 116 Still there are many challenges, such as which type of stem cells is most suitable to achieve optimal immunosuppression and tissue healing. Further studies are also needed to standardize and determine optimal dosing and where in the conventional treatment algorithms this therapy should be placed.…”

Section: Resultsmentioning

confidence: 99%

Inflammatory Bowel Diseases: Current Therapeutic Approaches and Potential of Using Stem Cells

Srivastava¹

2017

JSRT

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Inflammatory bowel diseases (IBDs) are chronic and progressively deteriorating in nature without many promising curative treatments. Chronic inflammation of not well defined origins is considered to be the root cause of the problem which affects intestinal mucosa with or without transmural involvement. IBDs are divided in two main categories: Crohn's disease (CD) and ulcerative colitis (UC). While there is no long lasting cure for IBDs, current therapies can only reduce the causative inflammatory process with the hope to induce long-term remission. Treatment modalities for the IBDs are still evolving. The increased understanding of the underlying immunopathology has helped identify new targeted treatment options like immunosuppressive antibodies directed against signaling molecules. Use of stem cells, which are capable of modulating the immune system, can offer a long lasting relief to the patients suffering from the disease. The goal for stem cell-based therapy is to achieve long lasting cure, if not a permanent one. To achieve this, it would be desirable to obtain cell types, whether genetically modified or naturally occurring, having a high migratory ability in addition to homing ability into the afflicted parts of intestine. These cells should also have high in vivo survival potential, and then be able to regulate the immune reaction without provoking any response from the host's immune system and repair the injured tissue. Hematopoietic stem cells (HSC) and mesenchymal stromal cells (MSC) therapies are being investigated as a treatment for IBDs. MSC therapy is well tolerated and has minimal established side-effects compared to HSC therapy, which involves ablative chemotherapy. Several clinical studies using MSCs have been initiated and some early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, which can be resolved only by scientifically unveiling the mechanisms of therapeutic action of stem cells. In this review, we summarize current therapies for IBDs and recent advances in the field of stem cell therapy, which offer promise to become the next generation treatment of choice.

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“…In a phase II trial, 15 patients with refractory active luminal CD were treated with allogeneic MSCs for 4 weeks. After 6 weeks, there was a reduction of the mean CDAI scores and improvement of mean quality of life scores in patients with luminal CD refractory to biologic therapy (32). The probably most important work in this field is a large (330 patients enrolled), multicenter, randomized, double-blind, phase III trial generated by Osiris Therapeutics.…”

Section: Mesenchymal Stem Cell Transplant (Msct) In Ibdmentioning

confidence: 99%