Gastro-Intestinal Committee

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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

  • Assist in the planning of the annual meeting scientific program and the review of submitted abstracts in the Solid Organ Targeted Therapy & Tissue Engineering categories.
  • Review the status of the regenerative medicine field and foster international discussion about controversies in the field of regenerative medicine for digestive diseases. 
  • Publish position papers and engage in scientific discourse as necessary to advance the field.

 

Upcoming Events:

  • ISCT Gastrointestinal Scientific Committee Co-Chair, Rachele Ciccocippo, to present at the 15th Congress of the European Crohn's and Colitis Organisation 13 February, 2020 in Vienna, Austria (https://www.ecco-ibd.eu/ecco20.html)
  • ISCT Gastrointestinal Scientific Committee to host a Hot Topic Session "Regenerative Medicine in Digestive Diseasess: State of the Art, Open Needs and Next Steps" at ISCT 2020 Paris 28 May, 2020. For full program details and to register visit http://www.isct2020.com/.

 

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.)

 

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 the current feature article(s) and accompanying review see below:

Posted March 2020

Report of the 15th European Crohn’s and Colitis Organisation Annual Congress: what’s boiling on stem cells and advanced therapies in inflammatory bowel diseases.

Rachele Ciccocioppo1 & Giuseppe Orlando2

1Gastroenterology Unit, Department of Medicine, AOUI Policlinico G.B. Rossi & University of Verona (Italy); 2Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem (North Carolina - USA).

Dear Reader,

On February 12-15, the annual congress of the European Crohn’s and Colitis Organisation (Vienna, Austria) was attended by more than 8,000 delegates from 87 different countries, thus becoming the leading world congress on Inflammatory Bowel Diseases. The overarching theme was “Inflammatory Bowel Disease: beyond 2020”, and the main sessions covered a wide range of topics addressing strategies to reduce disease burden and to achieve a better patient stratification, the future of biological therapies, as well as the challenge of the surgery approach, in addition to presentations of clinical cases and several interesting debates. Nonetheless, only two short talks included in two sponsored symposia addressed the topic of cell therapies. Specifically, the first was entitled “Stem cells in action,” presented by Dr. I. White from Israel at a Satellite Symposium sponsorised by Takeda, and the second was entitled “Beyond biologics: the role of stem cell therapies”, presented by Rachele Ciccioppo at a Satellite Symposium sponsorised by Biogen Samsung Bioepis. It is arguable that advanced medicinal therapies do not draw much attention. Therefore, we should ask ourselves the reasons for this, whether it is a matter of low awareness by researchers/clinicians, the results published so far are not convincing, or whether there is scarce interest from Industry. Answering these questions may help us to better understand the hurdles these new therapies are encountering in the real world, identify the right initiatives in order to highlight their real potential, and offer patients with a different chance of treatment.

The scientific program also included oral and poster presentations of the best abstracts, whose number achieved a total of 1014, as published on the Journal of Crohn’s and Colitis Abstract Book volume 14/S1 2020. Among these, only five abstracts (0.49%) covered the topic our community is interested in. In particular, the abstract #DOP84 entitled “Crohn’s disease modifies the DNA methylome of human adipose-stem cells, which is only partially re-established in remission” from a Spanish group based in Terragona and Barcelona, showed that stem cells harvested from mesenteric adipose tissue of Crohn’s patients exhibit a dysfunctional phenotype due to epigenetic modifications characterised by an altered DNA-methylation pattern and gene expression profile. Remarkably, this phenotype persists in patients in remission, and are found in all adipose depots including subcutaneous fat. This evidence has potential resonance on both scientific and clinical grounds since understanding how the disease impacts stem cells is crucial when investigating the complex pathophysiology of mechanisms leading to tissue injury, as well as for the success of cell-based therapies.

The following abstract #DOP85 entitled “The role of fibroblasts in the pathogenesis of Crohn’s disease-associated fistulas and in mesenchymal stem cell therapy” from a Dutch group, despite the title including the term ‘mesenchymal stem cell therapy,’ did not address this topic, since the authors analysed the mRNA profile of fibroblasts isolated from both Crohn’s perianal fistulas and normal colonic mucosa without finding any substantial difference. However, they found that 20 most significant differentially expressed genes between Crohn’s fistulas and normal colon fibroblasts were genes related to epithelial-mesenchymal transition, cell migration and nuclear factor-κB signalling pathway. Notably, these pathways play a crucial role in the pathogenesis of perianal fistulas in Crohn’s disease [1]. Furthermore, co-culture experiments carried out with Crohn’s fistula-derived fibroblasts, showed increased differentiation and proliferation rates of CD25+FoxP3+ Treg cells, thus shedding some light on the role of fibroblasts in this condition that may help in directing new therapeutic strategies.

A more direct interest on stem cells is held in the abstract #P080 entitled “Therapeutical effect of urine-derived stem cells on dextran sulphate sodium DSS-induced chronic model of mice” from a Chinese group. The authors stated that the urine stem cells may be harvested in a safer and non-invasive way in comparison with those isolated from bone marrow or adipose tissue, and also at lower cost. This is why they isolated these stem cells from urine samples of three young adult men that, after biological characterization showing hallmarks of mesenchymal stem cells, were successfully used by systemic infusions to treat an experimental animal model of chronic colitis.

The abstract #P617 “Mesenchymal stromal cells of bone marrow reduce the risk of post-operative recurrence of Crohn’s disease” from a Russian group was focused on MSC. Here, 36 patients who had undergone ileocecal resection were divided into two groups: one receiving mesenchymal stromal cells and one Mesalazine 4 gr/day with a follow-up period of 5 years. The results showed a statistically significant difference at 2 and 5 years of the C-reactive protein level and the relapse rate between the two groups, favoring the use of cell therapy. Unfortunately, no specification of the dosage of cells, the route of administration used (possibly intravenous), the number of infusions and the interval between them are specified.

Last but not least, we would like to mention the abstract #P064 entitled “Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism” from another Chinese group. Here, systemic infusions of exosomes derived from human bone marrow-mesenchymal stromal cells resulted in a better outcome of dextran sulphate sodium-induced colitis in mice than saline solution. More in depth, cell treatment was able to downregulate inflammation, preserve intestinal barrier and polarise macrophage towards a regulatory phenotype. The latter appeared as the main mechanism since depletion of macrophages inhibited the benefit. This work is very interesting considering the ability of mesenchymal stromal cells to favour a shift towards a regulatory phenotype of intestinal macrophages and to overcome experimental colitis has been already published [2]. Thus, it seems conceivable that exosomes retain the immunodulatory effects of their cellular counterpart. Furthermore, this work paves the way for phase I-II clinical studies aimed at inhibiting/reverting intestinal inflammation in Crohn’s disease.

We may conclude that there is the need for a call of action to increase the knowledge on these kinds of advanced therapies, to perform well-designed, consistent and informative studies, trying to address not only clinicans and researchers, but also industries that have the power to push the development of these therapies. This represents the core business of our Committee and we all are responsible for the advancement of this field.

References

  1. Panés J, Rimola J. Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol 2017;14:652-664.
  2. Anderson P, Souza-Moreira L, Morell M, Caro M, O’Valle F, Gonzalez-Rey E, Delgado M. Adipose-derived Mesenchymal Stromal Cells Induce Immunomodulatory Macrophages Which Protect From Experimental Colitis and Sepsis. Gut 2013;62:1131-1141.

 

Featured Publication Archive:

 


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

 

 

Mattia Algeri, MD
Ospedale Pediatrico Bambino Gesù
Rome, Italy
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
Vincenzo Cardinale, MD, PhD
Sapienza University of Rome
Rome, Italy
  
Francesco Dazzi, MD
King’s College London
London, United Kingdom
Paolo De Coppi, MD, PhD
National Institute for Health Research
London, United Kingdom
  
Claudia Dos Santos, MD, MSc
University of Toronto
Toronto, ON, Canada 
Eleuterio Lombardo, PhD
Takeda Madrid, Cell Therapy Technology Center 
  
Basak Uygun, PhD
Harvard Medical School
Boston, MA, United States
 

 

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