Our field of research has taken advantage of recent tools for genetic engineering that have opened us new perspectives and we all look forward to seeing faster advances and achievements.
This year, we will meet for the TTS congress in Madrid, from June 30th to July 5th, where workshops and sessions on xenotransplantation will allow us to be updated on the latest developments. I invite all members to join this important venue and to share their most recent data.
I also would like to suggest you to submit your work to our journal “Xenotransplantation” which has reached the impact factor of 3.96. In contrast to other journals, we accept clinical case-reports and are confident that the impact of our field will continue to grow!
I look forward to seeing you in Madrid,
Leo Buhler IXA President
The German Xenotransplantation Research Cluster “Biology of xenogeneic cell, tissue and organ transplantation – from bench to bedside”
Eckhard Wolf, Bruno Reichart Speakers of the DFG-funded Transregional Collaborative Research Center 127 (TRR127)
The TRR127 is a unique Consortium encompassing basic research on xenogeneic immune mechanisms, generation and evaluation of novel genetically (multi-) modified donor pigs, and preclinical porcine islet, heart valve, and heart transplantation studies. The collaboration of institutions from the Ludwig-Maximilian University Munich, the Technical University Munich, the Hannover Medical School, and the Technical University Dresden is funded by the German Research Council (DFG). Additional participating institutions are the Friedrich Loeffler Institute (Mariensee), the German Primate Centre (Göttingen), the Robert Koch Institute (Berlin), and the Paul Ehrlich Institute (Langen).
The Consortium is structured as three closely interacting Research Areas, supported by Central Projects that focus on ethical, legal and societal issues, microbiological safety, provision of safe donor pigs with effective genetic modifications, and non-human primate (NHP) studies (Fig. 1).
Fig. 1. Structure of the DFG-funded Transregional Collaborative Research Center 127 – TRR127
The five projects in Research Area A investigate and modulate immune mechanisms at the xenograft-host interface. Modifications on the xenograft side include expression of the negative costimulatory molecule PDL1, down-regulation of porcine MHC (SLA) molecules, and expression of pro-angiogenic, anti-inflammatory and anti-thrombotic factors. Modifications on the recipient side target the instant blood-mediated inflammatory reaction (IBMIR) observed after intraportal xeno-islet transplantation. A novel non-lymphopenic humanised mouse model is used for detailed analyses of cellular and non-cellular components of IBMIR. In addition, xenograft-specific regulatory T cells will induce long-lasting xenograft tolerance.
The three projects in Research Area B develop genetically modified donor pigs to overcome rejection and improve graft function. These genetic modifications include elimination of major xenoantigens such as αGal, Neu5Gc and Sd(a), expression of transgenes to combat cellular (LEA29Y, PDL1) and humoral (complement regulators) rejection and to protect the graft (A20, heme oxygenase 1, human thrombomodulin). Another goal is generation of PERV-free donor pigs.
Three projects in Research Area C investigate preclinical islet xenotransplantation. Diabetic mouse models and NHPs are used to test pancreatic islets/beta cells from different sources: wild-type porcine/human islets, stem cell-derived beta cells, and novel genetically modified porcine islets. The Beta-O2 macroencapsulation device will be further improved and a clinical trial is planned. A fourth project provides a platform for studying xenogeneic activation of complement and coagulation. Pertinent assays for NHPs will be developed. These are important for a project that aims to provide cell-free porcine heart valves that lack major xenoantigens. Another project deals with heart transplantation: novel genetic modifications are first evaluated by ex vivo perfusion of organs with human blood in a bi-ventricular system. The most promising genetic modifications then proceed to orthotopic transplantation experiments in baboons using oxygenated cardioprotective solution and anti-CD40/PASylated anti-CD40L based immunosuppression.
Our Consortium is very pleased to host the 2019 IXA Conference in Munich, Germany. We kindly invite you to visit us and share with us the enthusiasm of moving xenotransplantation to clinical application.
IXA Vanguard Committee update
The 27th International Congress of The Transplantation Society will be held in Madrid, Spain from June 30-July 5, 2018 and the IXA will be well represented by several informative lectures on topics of great interest to our members. We hope to see many members in attendance at these and other events to show support for our colleagues and to take advantage of prime networking opportunities available.
Sunday July 1st (9:00-13:00)
Pre-Congress Workshop, entitled Xenotransplantation: Advancing to the Clinic. A pre-Congress workshop will be held on Sunday morning, July 1st, entitled Xenotransplantation: Advancing to the Clinic. This workshop will highlight the significant progress over the last 5 years in large animal models of cell and organ xenotransplantation and the outlook for the first clinical trials, topics that will certainly generate enthusiasm from its participants.
Monday, July 2nd (16:30-17:30)
A Campfire Session on: New Approaches in Xenotransplantation.
Monday, July 2nd will include a Campfire session on New Approaches in Xenotransplantation chaired by Drs. David KC Cooper, a past president and honorary member of IXA, and Kazuhiko Yamada, a former IXA Councilor. Lectures will be presented on several topics of great interest to our members including progresses made in solid organ xenotransplantation and novel therapeutic approaches aimed at overcoming xeno-rejection.
Tuesday, July 3rd (8:30-9:30)
Morning Symposia on: Issues relating to Clinical Xenotransplantation.
A Tuesday morning, July 3rd, Symposium on issues relating to clinical xenotransplantation will address the importance of genetically engineered pigs in advancing organ xenotransplantation as well as a discussion on recent developments in islet encapsulation strategies compared to free porcine islet xenotransplantation. The importance of the pig in xenotransplantation insures that these lectures will be highly informative and well attended.
Wednesday July 4th (14:30-16:00)
State-of-the-Art Session: Clinical Xenotransplantation – How close are we?
On July 4th, a State-of-the-Art session will address how close we are to bringing xenotransplantation into the clinic. Lectures by world-leaders will focus on kidney, islet and heart transplantation.
Please take the time to look over the online program for the Congress and consider registering to attend any of the many additional events that are available to satisfy a wide-range of interests.
Join a session that targets your area of expertise or step outside of the box and be exposed to new ideas that can spark your imagination. We look forward to seeing you in Madrid.