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News

Registration is open for the VANGUARD workshop on ethics in regenerative medicine

January 12, 2022 No Comments

Registration is now open for VANGUARD’s Online Workshop on the topic of Ethics in regenerative medicine. The event will take place on Thursday the 3rd of February 2022 and start at 16:00 CET.

A panel of experts will discuss ethical challenges that arise with the arrival of bio-engineered organs:

  • How can first-in-human clinical trials be conducted in a safe and responsible manner?
  • What are ethical points to consider for early clinical trials of regenerative medicine in transplantation?

You will have the chance to hear from the key opinion leader in the area of ethics in biomedicine, Professor Jonathan Kimmelman from McGill University.

The workshop will also include insights from the three ongoing projects on regenerative medicine:

  • BRAVE – Biomechanics and regenerative medicine for a one-shot treatment
  • OrganTrans – Controlled Organoids transplantation as enabler for regenerative medicine translation
  • VANGUARD – Bioartificial Pancreas to Cure Type 1 Diabetes

To conclude the meeting, a panel discussion moderated by Dr. Emma Massey (Erasmus Medical Centre) will bring together Prof. Kimmelman, Dr. Antonia Cronin (King’s College London), and Dr. Ekaterine Berishvili (University of Geneva) to further discuss ethical aspects in regenerative medicine.

Please note that registration in advance is required.

Research article: Efficient and safe correction of hemophilia A by lentiviral vector-transduced BOECs in an implantable device

December 14, 2021 No Comments

A new VANGUARD research article on Efficient and safe correction of hemophilia A by lentiviral vector-transduced BOECs in an implantable device has been published in Molecular Therapy, Methods & Clinical Development. The full article can be read online: https://doi.org/10.1016/j.omtm.2021.10.015

Abstract: Hemophilia A (HA) is a rare bleeding disorder caused by deficiency/dysfunction of the FVIII protein. As current therapies based on frequent FVIII infusions are not a definitive cure, long-term expression of FVIII in endothelial cells through lentiviral vector (LV)-mediated gene transfer holds the promise of a one-time treatment. Thus, here we sought to determine whether LV-corrected blood outgrowth endothelial cells (BOECs) implanted through a prevascularized medical device (Cell Pouch) would rescue the bleeding phenotype of HA mice. To this end, BOECs from HA patients and healthy donors were isolated, expanded, and transduced with an LV carrying FVIII driven by an endothelial-specific promoter employing GMP-like procedures. FVIII-corrected HA BOECs were either directly transplanted into the peritoneal cavity or injected into a Cell Pouch implanted subcutaneously in NSG-HA mice. In both cases, FVIII secretion was sufficient to improve the mouse bleeding phenotype. Indeed, FVIII-corrected HA BOECs reached a relatively short-term clinically relevant engraftment being detected up to 16 weeks after transplantation, and their genomic integration profile did not show enrichment for oncogenes, confirming the process safety. Overall, this is the first preclinical study showing the safety and feasibility of transplantation of GMP-like produced LV-corrected BOECs within an implantable device for the long-term treatment of HA.

VANGUARD presented at the SFT Congress

December 10, 2021 No Comments

Our coordinator Ekaterine Berishvili took a part in the 2021 Société Francophone de Transplantation (SFT) on December 8 to explain the challenges and to share the progress that was made during the first year and a half of the VANGUARD project.

The SFT congress is now an established event with a 20 years-long tradition. This is the first time after 10 years that the SFT is taking place in Switzerland.

Geneva was a natural choice for the organisation of this year’s SFT Congress, as the Geneva and Lausanne University Hospitals represent a cluster of knowledge with their world-renowned transplantation activities.

We look forward to the next annual Congress in Lyon, on December 13-16 2022.

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

October 26, 2021 No Comments

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

October 25, 2021 No Comments

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

June 11, 2021 No Comments

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

September 15, 2020 No Comments

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.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874700

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