VISICORT publication in the Official Journal of the Transplantation Society

Congratulations to the team! VISICORT PIs and researchers spanning the consortium have recently released a new paper in the Official Journal of the Transplantation Society. The paper entitled: “High-Risk Corneal Transplantation, Recent Developments and Future Possibilities” was released 22 August 2019. Authors are W. John Armitage, PhD; Christine Goodchild, MD; Matthew D. Griffin, DMed; David J. Gunn, FRANZCO; Jesper Hjortdal, DMSc; Paul Lohan, PhD; Conor C. Murphy, PhD; Uwe Pleyer, MD; Thomas Ritter, PhD; Derek M. Tole, FRC Ophth; Bertrand Vabres, MD.

Abstract: “Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.”

Find this and all of the other VISICORT publications here.

New VISICORT publication from NUI Galway team

“TNF-α/IL-1β-licensed mesenchymal stromal cells promote corneal allograft survival via myeloid cell-mediated induction of Foxp3+ regulatory T cells in the lung” was published online in the FASEB Journal on May 20, 2019. The authors of the study from NUI Galway are Nick Murphy, Oliver Treacy, Kevin Lynch, Maurice Morcos, Paul Lohan, Linda Howard, Gerry Fahy, Matthew D. Griffin, Aideen E. Ryan, and Thomas Ritter.

Congratulations to the team!

FASEB J. 2019 May 20:fj201900047R. DOI: 10.1096/fj.201900047R. [Epub ahead of print]

New VISICORT study in Frontiers in Immunology

A new study has just been published by VISICORT researchers in the leading open access journal Frontiers in Immunology today, 20 November 2018. The study “Third-party allogeneic mesenchymal stromal cells prevent rejection in a pre-sensitized high-risk model of corneal transplantation” was completed by the National University of Ireland Galway team of Paul Lohan, Nick Murphy, Oliver Treacy, Kevin Lynch, Maurice Morcos, Bingling Chen, Aideen E. Ryan, Matthew D. Griffin and Thomas Ritter.

The study shows for the first time that intravenous administration of third-party allogeneic mesenchymal stromal cells (MSC from neither the new cornea recipient nor the cornea donor) results in distinct immune modulatory effects that overcome pre-existing anti-donor immunity to prolong rejection-free survival of corneal allografts in a laboratory model of high-risk corneal transplantation. The experimental cell therapy regimen described in the paper appears to be compatible with prior cryo-preservation and with co-administration of a relevant immunosuppressive drug. These findings open the door to clinical translation of “off-the-shelf” allogeneic MSC products for recipients of high-risk corneal transplants who continue to suffer from very poor long-term graft survival rates. The results of this experimental study have formed the basis of a regulatory submission for the VISICORT Phase Ib clinical trial in patients receiving a second or greater transplant who are at high risk of rejection. This trial will determine the safety and feasibility of co-administration of allogeneic MSC and MMF in the setting of high-risk corneal transplantation.

VISICORT study published in Stem Cells

A VISICORT study was published recently in Stem Cells. The body of research entitled “Inter‐Species Incompatibilities Limit the Immunomodulatory Effect of Human Mesenchymal Stromal Cells in the Rat” by Paul Lohan, Oliver Treacy, Maurice Morcos, Ellen Donohoe, Yvonne O’Donoghue, Aideen E Ryan, Stephen J Elliman, Thomas Ritter and Matthew D Griffin was accepted for publication on 13 April 2018.

Abstract:

Mesenchymal stem/stromal cells (MSC) are an immunomodulatory cell population which are under pre‐clinical and clinical investigation for a number of inflammatory conditions including transplantation. In this study, a well‐established rat corneal transplantation model was used to test the ability of human MSC to prolong corneal allograft rejection‐free survival using a pre‐transplant intravenous infusion protocol previously shown to be efficacious with allogeneic rat MSC. Surprisingly, pre‐transplant administration of human MSC had no effect on corneal allograft survival. In vitro, human MSC failed to produce nitric oxide and upregulate IDO and, as a consequence, could not suppress rat T‐cell proliferation. Furthermore, human MSC were not activated by rat pro‐inflammatory cytokines. Thus, interspecies incompatibility in cytokine signalling leading to failure of MSC licensing may explain the lack of in vivo efficacy of human MSC in a rat tissue allotransplant model. Inter‐species incompatibilities should be taken into consideration when interpreting pre‐clinical data efficacy data in the context of translation to clinical trial.

VISICORT publishes in Frontiers in Immunology

The paper ‘Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?’ is based on the work of Dr Paul Lohan, Dr Oliver Treacy, Prof Matthew Griffin, Prof Thomas Ritter and Dr Aideen Ryan of the National University of Ireland Galway. The publication appears in the November 24, 2017, edition of Frontiers in Immunology. This research was funded by VISICORT, amongst other sources. Read the entire manuscript here.

Front. Immunol., 24 November 2017

https://doi.org/10.3389/fimmu.2017.01626

VISICORT partners involved in exciting new stem cell project

VISICORT partners NUI Galway, Orbsen, and Pintail are involved in NEPHSTROM, a new European project, which was launched last week. NEPHSTROM involves eleven partners from Ireland, the UK, Germany, and the Netherlands, and has received €6 million funding under the European Union’s Horizon 2020 funding programme. NEPHSTROM will evaluate the clinical safety and efficacy of a next-generation cell therapy discovered by Galway-based Orbsen Therapeutics, to combat diabetic kidney disease. Find out more about the project at www.nephstrom.eu.

VISICORT abstract accepted for oral presentation at ESBB’s 2014 Annual Conference, Leipzig

VISICORT have had an abstract accepted for oral presentation at ESBB’s 2014 Annual Conference. The ESBB conference will take place in Leipzig, Germany from Tuesday 21st to Friday 24th October.

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Launch of VISICORT

Welcome to the VISICORT Project.  We are very excited to be launching the project in April 2014.

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