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New Publication: Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells

VANGUARD partners from  UNIGE have published a new review article on Mechanisms of Immunomodulation and Cytoprotection Conferred to Pancreatic Islet by Human Amniotic Epithelial Cells in Stem Cell Reviews and Reports. The article is available open access and can be read here: https://link.springer.com/article/10.1007/s12015-021-10269-w

Abstract

Inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. Human amniotic epithelial cells (hAECs) possess regenerative, immunomodulatory and anti-inflammatory properties. We hypothesized that hAECs could protect islets from cellular damage induced by pro-inflammatory cytokines. To verify our hypothesis, hAEC monocultures, rat islets (RI), or RI-hAEC co-cultures where exposed to a pro-inflammatory cytokine cocktail (Interferon γ: IFN-γ, Tumor necrosis factor α: TNF-α and Interleukin-1β: IL-1β). The secretion of anti-inflammatory cytokines and gene expression changes in hAECs and viability and function of RI were evaluated. The expression of non-classical Major Histocompatibility Complex (MHC) class I molecules by hAECs cultured with various IFN-γ concentrations were assessed. Exposure to the pro-inflammatory cocktail significantly increased the secretion of the anti-inflammatory cytokines IL6, IL10 and G-CSF by hAECs, which was confirmed by upregulation of IL6, and IL10 gene expression. HLA-G, HLA-E and PDL-1 gene expression was also increased. This correlated with an upregulation of STAT1, STAT3 and NF-κB1gene expression levels. RI co-cultured with hAECs maintained normal function after cytokine exposure compared to RI cultured alone, and showed significantly lower apoptosis rate. Our results show that exposure to pro-inflammatory cytokines stimulates secretion of anti-inflammatory and immunomodulatory factors by hAECs through the JAK1/2 – STAT1/3 and the NF-κB1 pathways, which in turn protects islets against inflammation-induced damages. Integrating hAECs in islet transplants appears as a valuable strategy to achieve to inhibit inflammation mediated islet damage, prolong islet survival, improve their engraftment and achieve local immune protection allowing reducing systemic immunosuppressive regimens.

VANGUARD researchers awarded at the IPITA 2021 Virtual Congress

IPITA is the international pancreas and islet transplant association and the VANGUARD project had the honour to present its research findings at the 2021 Virtual Congress that took place on 20-23 October.

The conference enabled the scientists to connect with experts from both the industry and research. Between other things, the content of the Virtual Congress 2021 was structured around the updates on state-of-the-art research and around the clinical data results. During these three days, the participants had the chance to present their findings, actively discuss, and share their knowledge on diabetes and transplant-related topics.

We are proud to announce that Kevin Bellofatto and Fanny Lebreton (University of Geneva), and Antonio Citro (Hospital San Raffaele) have won the Best Oral Abstract and Best Poster Abstract awards.

We are looking forward to sharing new findings again the next year.

New VANGUARD infographic available

To introduce the VANGUARD project in easier to understand terms we have developed an infographic to explain the complex research happening in VANGUARD in a visual form.

New publications from the UNIGE group

VANGUARD is generating its first scientific outcomes, as seven works from the UNIGE group have recently been accepted and published in various journals such as Transplant International, Current Diabetes Report and Stem Cell Reviews and Reports:

Alibashe-Ahmed M, Berney T, Giovannoni L, Berishvili E (2020). Targeting Toll-Like Receptor 4: a promising strategy to prevent type 1 diabetes occurrence or recurrence. CellR4; 8: e2850.

Berishvili E, Kaiser L, Cohen M, Berney T, Scholz H, Floisand Y, Mattsson J (2020). Treatment of COVID-19 Pneumonia: the Case for Placenta-derived Cell Therapy. Stem Cell Reviews and Reports.

Berney T, Berishvili E (2020). I’ve got you under my skin. Nature Metabolism: News & Views.

Lebreton F, Wassmer CH, Bellofatto K, Berney T, and Berishvili E (2020). Organoïdes sécréteurs d’insuline : des «super-îlots» comme premier pas vers le pancréas bioartificiel. Med Sci (Paris), Volume 36, Number 10.

Wassmer CH, Bellofatto K, Perez L, Lavallard V, Cottet-Dumoulin D, Ljubicic S, Parnaud G, Bosco D, Berishvili E, Lebreton F (2020). Engineering of Primary Pancreatic Islet Cell Spheroids for Three-dimensional Culture or Transplantation: A Methodological Comparative Study. Cell Transplantation.

Wassmer CH, Berishvili E (2020). Immunomodulatory Properties of Amniotic Membrane Derivatives and Their Potential in Regenerative Medicine. Current Diabetes Reports volume 20, Article number: 31.

Wassmer CH, Lebreton F, Bellofatto K, Bosco D, Berney T, Berishvili E (2020). Generation of insulin-secreting organoids: a step toward engineering and transplanting the bioartificial pancreas. Transpl Int. 2020 Aug 27. doi: 10.1111/tri.13721.

The updated list of publications with hyperlinks can be found in the Outcomes section.

Information for patients and their relatives

Dear followers of the VANGUARD project,

Since the VANGUARD website has been activated, we have received many messages from patients and their families enquiring about the possibility to enroll in the study.

We are grateful to have so many people interested in the project and following our progress. At the same time, we feel a great responsibility toward people living with type 1 diabetes and their families.

At this time, we are at the very start of the VANGUARD project. We have had a small delay in getting started due to the COVID-19 pandemic. In the coming years we will work on developing the individual parts of the VANGUARD product. Once the separate parts are ready, we will assemble them to form the complete bioartificial pancreas. In order to understand whether the individual parts and the assembled product work, we will carry out our research on small animals. This development phase will take 5 years. After this we hope to start studying how the bioartificial pancreas works in humans/people.

Before we can test the bioartificial pancreas in humans, we need to show that it works (i.e. that it effectively produces insulin) and that it is safe to use in humans. The whole VANGUARD consortium is committed to meet these challenges.

As part of this project we will be investigating the patient perspective on this product. What are patients’ thoughts, concerns or information needs? We will study this so we can take these things into consideration in the next phase of human testing. When we start this part of our research, we will post information on how you can participate on our social media platforms. We hope you will get involved!

In the meantime, we will post news on the VANGUARD project on our social media platforms to keep you informed on our progress and the milestones we have reached.

Thank you for your interest in the VANGUARD project and be assured that the whole VANGUARD team is committed to deliver the bioartificial pancreas for you in the hope of offering a new treatment for Type I diabetes in the future.

Ekaterine Berishvili, MD, PhD, project coordinator

On behalf of the VANGUARD consortium

New article published on Immunomodulatory Properties of Amniotic Membrane Derivatives and Their Potential in Regenerative Medicine

The VANGUARD coordinator, Ekaterine Berishvili together with Charles-Henri Wassmer have recently published a new article in Current Diabetes Reports on the Immunomodulatory Properties of Amniotic Membrane Derivatives and Their Potential in Regenerative Medicine.

Purpose of Review

During the last decades, the field of regenerative medicine has been rapidly evolving. Major progress has been made in the development of biological substitutes applying the principles of cell transplantation, material science, and bioengineering.

Recent Findings

Among other sources, amniotic-derived products have been used for decades in various fields of medicine as a biomaterial for the wound care and tissue replacement. Moreover, human amniotic epithelial and mesenchymal cells have been intensively studied for their immunomodulatory capacities.

Summary

Amniotic cells possess two major characteristics that have already been widely exploited. The first is their ability to modulate and suppress the innate and adaptive immunities, making them a true asset for chronic inflammatory disorders and for the induction of tolerance in transplantation models. The second is their multilineage differentiation capacity, offering a source of cells for tissue engineering. The latter combined with the use of amniotic membrane as a scaffold offers all components necessary to create an optimal environment for cell and tissue regeneration. This review summarizes beneficial properties of hAM and its derivatives and discusses their potential in regenerative medicine.

Read the full article online: https://link.springer.com/article/10.1007/s11892-020-01316-w

New research on a promising treatment against type 1 diabetes funded by the European Commission

More than 40 million individuals worldwide are affected by type 1 diabetes, which is the most common chronic disease in children and adolescents. Today’s primary treatment for diabetes is insulin therapy, which requires multiple injections every day to control a person’s blood sugar levels. This can potentially lead to chronic complications such as kidney-related issues (nephropathy), visual impairments (retinopathy) and ischemic heart disease. Beta-cell replacement, done either by pancreas or islet transplantation, is a valid alternative to daily injections, as it restores the possibility to control blood sugar levels (glucose). However, pancreas or islet transplantations rely on organ donors and require lifelong anti-rejection medication to avoid the rejection of the transplanted organ or cells. The process is also associated with complications and is currently only offered to a limited number of patients with severe forms of the disease.
Within the framework of a European funded H2020 project, VANGUARD aims to develop a cure for type 1 diabetes available to a larger group of patients. The VANGUARD project will use advanced tissue engineering techniques to generate a bioartificial pancreas, with the aim to propose a novel cell-based treatment to type 1 diabetes that overcomes the limitations inherent to current therapies. Working on this innovative solution is a multidisciplinary team of researchers from Switzerland, Italy, France, Germany and The Netherlands, led by Dr Ekaterine Berishvili from the University of Geneva, Department of Surgery. According to Dr. Berishvili “the VANGUARD multidisciplinary team will bring regenerative medicine for type I diabetes from bench to bedside”. In total, the project brings together outstanding expertise from six academic institutions with leading scientists in bioengineering, transplantation, gene therapy, immunology and ethics, two SMEs and an NGO.

VANGUARD’s bioartificial pancreas has the potential to improve the success rate of beta-cell replacement therapies with exceptional advantages in terms of efficacy and safety. The treatment of a large number of patients with type 1 diabetes could dramatically reduce the financial burden of the disease, mostly associated with the healthcare costs of chronic secondary complications of diabetes.

The VANGUARD project officially started and had its kick-off last month in January 2020, in conjunction with the annual symposium of the European Pancreas and Islet Transplant Association. Representatives from the nine project partners discussed the start of the research activities and the path towards what has the potential to be a real breakthrough towards a cure for type 1 diabetes.

Scientific contact

University of Geneva
Dr Ekaterine Berishvili
Researcher and Coordinator of the VANGUARD project
Department of Surgery
Faculty of Medicine
project@vanguard-project.eu

About VANGUARD

The VANGUARD project is funded by the European research and innovation program Horizon 2020 (project number 874700), under the Health program. It is a five-year project that officially started in January 2020 and will end in December 2024. It involves nine project partners from seven European countries and has a budget of € 6.8 million.
www.vanguard-project.eu