Gastro-Intestinal Committee

 Charter

The Gastrointestinal Committee strives to:

  • Assist in the planning of the annual meeting scientific program and the review of submitted abstracts in the Solid Organ Targeted Therapy- Pre-clinical/Clinical Studies category.
  • Review the status of the Gastroenterology field and compile a list of major scientific issues that must be addressed to advance or enable cellular therapies.
  • Publish position papers and engage scientific discourse as necessary to advance the field.

 

Projects and Objectives

  • Contribute to the ISCT Annual Meeting program.
  • Prepare a consensus paper defining clinical trial criteria for mesenchymal stem cell treatments in immune-mediated intestinal diseases (i.e Crohn’s disease, ulcerative colitis, celiac disease)

 

Message from the Co-Chair:

Dear Friends,

On last 6th-9th March, the 14th Congress of the European Crohn’s and Colitis Organization was held at the Bella Center in Copenhagen (Denmark). The number of participants reached the extraordinary number of 8,034 delegates from worldwide, thus witnessing the relevance of inflammatory bowel diseases, namely Crohn’s disease and ulcerative colitis, in the field of health. The total number of abstracts presented as oral or digital communications (no. 38 and 90, respectively) or poster (no. 861) was 989, of which only 21 (2.12%) were regarding the field of cell therapy and regenerative medicine. Specifically, three were about autologous hematopoietic stem cell transplantation in refractory luminal Crohn’s disease, while eight explored the use of intestinal organoids to investigate pathogenic pathways of mucosal damage or to establish an in vitro system to evaluate the effect of new therapeutic tools in order to avoid the use of animal models. Almost half of these 21 abstracts regarded mesenchymal stromal cells. Of course, additional data regarding the use of Darvadstrocel (an industrial preparation of allogeneic adipose tissue-derived mesenchymal stromal cells) in refractory fistulizing Crohn’s disease have been presented. Worth noting, the development of a registry (INSPIRE; EU PAS Register Number: EUPAS24267) aimed at establishing a framework to capture real-world clinical effectiveness and safety information of all patients treated with Darvadstrocel over 36 months has aroused interest. In an additional two studies, this new therapeutic strategy was applied in combination with a biological agent (certolizumab pegol in fistulizing Crohn’s disease, and adalimumab in ulcerative colitis) with promising results. Interestingly, even the frequency of Clostridial infection in patients with ulcerative colitis receiving mesenchymal stromal cells resulted significantly lower than in patients with ulcerative colitis receiving biological immunosuppressive preparations. For more details, please see the Abstract book (Journal of Crohn’s and Colitis 2019;13:S1-S555). In conclusion, although cellular therapies and, more in general, regenerative medicine are particularly suited for the use in chronic inflammatory conditions affecting the gut, we can realize that only a negligible percentage of abstracts presented at this relevant congress treats this topic. This implies that there is much work to do for us to improve the knowledge and accelerate the widespread use of cellular therapies for digestive diseases. We need to overtake the barriers among different medical disciplines through networking and favoring studies in this specific and upfront field. So we have to connect, communicate, and translate!!!

Sincerely,

Rachele Ciccocioppo

 

Featured Publication:

One of the ISCT Gastrointestinal (GI) Committee's main objectives is to increase awareness of advanced cell & gene therapies in the field of the digestive system and promote the safe and effective use of these medicinal therapies for the safety of patient's worldwide. To help achieve this goal, the ISCT GI Committee conducts regular literature reviews and selects novel research to be featured alongside a critical analysis developed by committee members. To view this month's featured article and accompanying review see below:

Antifibrogenic potential of mesenchymal stromal cells in treating fibrosis in Crohn’s disease. Digestive Diseases and Sciences 2018;63:1821–1834.

View Article

Dear Reader,

Crohn’s disease is a chronic inflammatory enteropathy that manifests through three phenotypes: inflammatory, structuring and penetrating. Rather than being three separate behaviours, they actually represent the natural progression of bowel damage, with epithelial-to-mesenchymal transition being a leading mechanism. Arguably, the structuring one is burdened by a high rate of hospitalization and surgical procedures due to a progressive fibrosis of gut wall leading to lumen obstruction. The number of resections may ultimately lead to functional impairment and short bowel syndrome, thus largely affecting patients’ quality of life. Despite the fact that the advent of biological therapies has dramatically changed the outcome of these patients, the benefit in terms of reduction of surgery rate is still limited. Therefore, there is a growing need for a better therapeutic approach, and mesenchymal stromal cells (MSCs) seem to be the best candidate in fulfilling this need. Up to now, either systemic or local administration of MSCs has been applied in both experimental models of colitis and clinical trials recruiting patients suffering from treatment-resistant inflammatory or fistulizing Crohn’s disease with promising results. However, no evidence on the putative ability of MSCs in limiting fibrosis has been collected so far. In this context, the study by Lian and coworkers, who investigated the preventive and therapeutic effects of MSCs in an experimental model of colonic fibrosis, carries novel information on both scientific and clinical grounds. Briefly, intestinal fibrosis was induced by treating Balb/c mice with increasing doses of 2,4,6-trinitrobenzene sulfonic acid enema over a period of seven weeks, and allogeneic bone marrow-derived MSCs were intravenously infused before or during the induction of colitis to test both their preventive and therapeutic efficacy. Notably, the prophylactic MSC treatment inhibited not only colon shortening, but also the accumulation of fibrotic tissue, the expression of fibrotic proteins and the epithelial-to-mesenchymal transition. On the other hand, the therapeutic use of MSCs reversed intestinal fibrosis and reduced the epithelial-to-mesenchymal transition. In addition, the study of the molecular and signaling pathways involved, showed a down-regulation of secretion of the fibrogenic factors transforming growth factor-b, interleukin (IL)-1b, IL-6 and IL-13 and an up-regulation of IL-10, an anti-fibrogenic and immunomodulant factor. In parallel, the phosphorylation of Smad2 and Smad3 was strongly reduced upon MSC administration, thus critically hampering the epithelial-to-mesenchymal transition. Besides the contribution to scientific knowledge, this work paves the way for a phase I-II clinical study aimed at inhibiting/reverting intestinal fibrosis, hence blocking the progression of tissue damage and the natural history of this invalidating condition. Should the results confirm the anti-fibrogenic action of MSCs against CD-associated fibrosis, the chance of safely and efficaciously treating this dreadful condition becomes a real prospect. Patients will have the opportunity to enjoy a safer and possibly more efficacious treatment, ultimately ameliorating their outcome and quality of life.

 

Prof. Rachele Ciccocioppo
Gastroenterology Unit, Department of Medicine
AOUI Policlinico G.B. Rossi & University of Verona
Piazzale L.A. Scuro, 10 – 37134 – Verona (Italy)
Tel. +39 045 8124578
Electronic address: rachele.ciccocioppo@univr.it

 


Committee Members:




Rachele Ciccocioppo, MD
Co-Chair (Jan 2018 – Dec 2019)
University of Verona
Verona, Italy

Giuseppe Orlando, MD, PhD
Co-Chair (Jan 2018 – Dec 2019)
Wake Forest University
Winston-Salem, NC, USA

 

 

Basak Uygun, PhD
Harvard Medical School
Boston, MA, United States

Khalil N. Bitar, PhD
Wake Forest Institute for Regenerative Medicine
Winston Salem, NC, United States

Alejandro Soto-Gutiérrez, MD, PhD
University of Pittsburgh
Pittsburgh, PA, United States

Paolo De Coppi, MD, PhD
National Institute for Health Research
London, United Kingdom

Daniel C. Baumgart, MD, PhD, MBA, FRCP
University of Alberta
Edmonton, AB, Canada

Daniel Leffler, MD, MS
Takeda Pharmaceutical Company Ltd.
Boston, MA, United States


Claudia Dos Santos, MD, MSc
University of Toronto
Toronto, ON, Canada


Francesco Dazzi, MD
King’s College London
London, United Kingdom

 

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