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)

 

Committee Publications:

Perspective of the International Society for Cell & Gene Therapy Gastrointestinal Scientific Committee on Intravenous Use of Mesenchymal Stromal Cells in Inflammatory Bowel Disease (PeMeGi). (Cytotherapy 2019 August; 21(8): 824-839)

Proceedings of the signature series event of the International Society for Cellular Therapy: "Advancements in cellular therapies and regenerative medicine in digestive diseases," London, United Kingdom, May 3, 2017. (Cytotherapy 2019 March; 20(3): 461-476.)

 

Message from the Co-Chair:

Dear Friends,

On March 6th-9th, 2019 the 14th Congress of the European Crohn’s and Colitis Organization was held at the Bella Center in Copenhagen (Denmark). Total participants reached the extraordinary number of 8,034 delegates from around the world, demonstrating the relevance of inflammatory bowel diseases, namely Crohn’s disease and ulcerative colitis, in the healthcare field.

The total number of abstracts presented as oral, digital or poster communications (no. 38, 90 and 861 respectively) totaled 989, of which only 21 (2.12%) were regarding the field of cell therapy and regenerative medicine. Specifically, three of these abstracts 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 set out 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 involved mesenchymal stromal cells.

Not surprisingly, additional data regarding the use of Darvadstrocel (an industrial preparation of allogeneic adipose tissue-derived mesenchymal stromal cells) in refractory fistulizing Crohn’s disease was 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, results showed the frequency of Clostridial infection in patients with ulcerative colitis receiving mesenchymal stromal cells was 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 regenerative medicine are particularly suited for use in chronic inflammatory conditions affecting the gut, only a negligible percentage of abstracts presented at this relevant congress address the topic. This implies that there is much work to be done to improve the knowledge and accelerate the widespread use of cellular therapies for digestive diseases. We need to overcome the barriers among different medical disciplines through networking and favoring studies in the specific and upfront field of regenerative medicine for gastroenterology. We have to connect, communicate, and translate!!!

Sincerely,

Prof. Rachele Ciccocioppo
Co-Chair, ISCT Gastrointestinal Committee

 

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, stricturing and penetrating. Rather than being three separate behaviours, these phenotypes actually represent the natural progression of bowel damage, with epithelial-to-mesenchymal transition being a leading mechanism. Arguably, the stricturing phenotype is burdened by a high rate of hospitalization and surgical procedures due to a progressive fibrosis of the gut wall leading to lumen obstruction. The number of resections may ultimately lead to functional impairment and short bowel syndrome, 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. 

In addition to the contribution to scientific knowledge, this work paves the way for a phase I-II clinical studies aimed at inhibiting/reverting intestinal fibrosis, hence blocking the progression of tissue damage and the natural history of this debilitating 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 – Present)
University of Verona
Verona, Italy

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

 

 

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

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

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

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

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

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


Eleuterio Lombardo, PhD
Takeda Madrid, Cell Therapy Technology Center
Madrid, Spain

Vincenzo Cardinale, MD, PhD
Sapienza University of Rome
Rome, Italy

 

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