Official Sections CTRMS ISVCA IPITA IPTA ISODP IRTA IXA SPLIT TID

Eckhard Wolf taps the ceremonial keg at the Hofbrauhaus.

Dankeschön to Eckhard Wolf (Congress Chair), Bruno Reichart (Program Chair) and all of the people that contributed to the success of the IXA Congress in Munich. The host city lived up to expectations and provided us with wonderful opportunities for social interactions and networking that will not soon be forgotten. Attendees should have received a link to a survey for the IXA2019 evaluation in their registered email. A link to the survey can also be found here.  Please take a few moments to respond as this will help to ensure that we continue to provide the best experiences for our members as we look ahead to TTS 2020 in Seoul, South Korea and the IPITA-IXA-CTRMS Joint Congress (2021) in San Diego, USA.

IXA Leadership

This year’s Congress marked the introduction of new IXA President Agnes Azimzadeh (USA), taking over from Past President Leo Buhler (Switzerland). We would like to thank Leo for the fantastic job he has done to enhance the prestige of the IXA under his guidance. Agnes has been an integral part of the IXA Council for the last eight years and we know that she will continue to move us forward to even greater heights.

Past President of IXA, Leo Buhler, and new President, Agnes Azimzadeh.

President's Message

Agnes Azimzadeh


Massachussets General Hospital and Harvard Medical School,
Boston, MA, United States

Dear Colleagues

It is with great pleasure and honor that I succeed Dr. Leo Buhler in his post of IXA President. Over the past two years, Dr. Buhler has uniquely contributed to the development of the International Xenotransplantation Association (IXA) and its Journal. On behalf of the Association, I wish to thank Dr. Buhler for his strong leadership. I look forward to continue the advancement of our society over the next two years.

Last October, the Ludwig Maximilian University in Munich hosted the 15th International Xenotransplantation Association Congress. The Congress was an outstanding success, both scientifically and socially. Thank you to Congress Chairs Eckhard Wolf and Bruno Reichart for developing a rich and forward-looking scientific program in a relaxing and historical atmosphere. The numerous scientific highlights of the meeting were summarized by Peter Cowan in the closing session and in the IXA Newsletter. This year’s meeting illustrated that the pace of progress in our field has accelerated over the last few years and that the timeline for clinical application is shortening.

After the Munich meeting the IXA Council met to discuss the state and direction of the association. The discussion was largely inspired and driven by the results of the recent member survey. I am very happy to report that the IXA Council has taken resolutions to create several new initiatives:

  1. The Young Investigator Committee (formerly called Vanguard Committee) will provide new mentorship opportunities for trainees.
  2. In an effort to further improve IXA communications, webinars and podcasts on Xenotransplantation will be developed and the website will be updated.
  3. Options were discussed to improve the visibility of the journal.
  4. A Young Investigators Endowment Research Fund (YIER) will be created to support the education, research and mentorship of the next generation of professionals in Xenotransplantation. The funds raised will support a variety of initiatives, such as travel awards and laboratory exchange programs to broaden the research experience of scholars. This fund will rely on your generous donations. Additional awards and fund-raising initiatives were discussed.
  5. While guidelines for heart, lung, islet and cornea xenotransplantation have been previously established and published, there is a paucity of information to guide kidney and liver clinical applications. The IXA Council will address this need in consultation with experts, by working towards the publication of guidelines for kidney xenotransplantation and xenogeneic liver as a bridge therapy. The IXA remains closely linked to the World Health Organization to review and develop guidelines and support Xenotransplantation across the globe.
  6. The Public Perception of Xenotransplantation was selected as one of the society’s priorities, and the IXA Council will actively work toward fostering the education of, and dialogue with, health professionals as well as the general public, in various countries.

These initiatives will rely on the dedicated and hard work of our vibrant IXA Council members. We will share further updates on the progress of these and other activities with you throughout the year.

Importantly, the realization of these goals relies in part on your contributions. I thank you for participating in our membership survey and providing useful and relevant comments and suggestions. I would like to encourage your continued contribution of ideas and suggestions to improve our society.

With my best wishes,

Agnes Azimzadeh
IXA President

IXA Council

We welcome Wayne Hawthorne as our new President-Elect, as well as three new Councilors.

Congratulations to all of our newly elected representatives who will join returning members Rita Bottino (USA), Pierre Gianello (Belgium), and Joseph A. Tector (USA). We would also like to take an opportunity to thank outgoing Councilors Curie Ahn, Muhammad Mohiuddin, and our most recent Past President Peter Cowan for their valuable contributions. They have set a high-bar for our new Council members!

Additionally, we would like to acknowledge the Chairs of several important standing committees.  Robin Pierson (USA) chairs the Ethics Committee and Christopher Burlak (USA), the Vanguard Committee.

Wayne Hawthorne - President-Elect (2019-2021)

Wayne Hawthorne (Australia) is Professor of Surgery at the University of Sydney and Director of the National Pancreas and Islet Transplant Laboratories for Australia’s Clinical Islet Transplant program. He is a Council Member of Scientific Program and Education Committee of the Transplantation Society of Australia and New Zealand as well as a former IXA Council member. His scientific interests include islet allotransplantation and xenotransplantation.

Shaoping Deng - Councilor (2019-2023)

Shaoping Deng, M.D., Prof. of Surgery (China), is President of Sichuan Provincial People’s Hospital (SPPH) in Chengdu. He has devoted his long and illustrious career to the research of organ transplantation and diabetes, including the transplantation of hepatocytes and pancreatic islets. Since he went back to China in 2009, he built a comprehensive organ and cell transplant program at SPPH, covering almost all organ (kidney, liver, pancreas, pancreas + kidney, heart, lung and small bowel) and cell (islet, stem cell) transplantation in clinic. He is well known for his openness in discussing new ideas, whether it is a method to improve hospital management to provide better care, fostering international collaborations, or advancing cell/organ xenotransplantation.

Burcin Ekser - Councilor (2019-2023)

Burcin Ekser (USA) is Assistant Professor of Surgery at Indiana University School of Medicine where he is the Director of the Xenotransplantation Research Laboratory. Throughout his career, he has been presented with numerous young investigator awards including those from the IXA and TTS. He is passionate about bringing xenotransplantation to the clinic. His research interests include genetic engineering and scaffold-free 3D bio printing.

Shuji Miyagawa - Councilor (2019-2023)

Shuji Miyagawa (Japan) is Associate Professor of Surgery at the Osaka University Graduate School of Medicine. He is the president of Japanese Society of Xenotransplantation. An expert in immunology, he is particularly interested in the advancement of xenotransplantation through the use of genetically engineered porcine tissues. He previously served as IXA councilor from 2013-2017 and has remained active in providing his expertise when called upon.

Highlights from Munich

Kazuhiko Yamada with Leo Buhler and Agnes Azimzadeh

Megan Sykes with David Sachs

Eckhard Wolf with Bruno Reichart

The IXA is proud to announce that our 15th Congress was attended by over 340 registrants from 25 countries.

Click here to visit www.ixa2019.org

The Carl-Gustav Groth Xeno Prize is awarded annually to the primary author of what is selected as the best paper submitted to Xenotransplantation each calendar year. The 2018 winner is Kazuhiko Yamada (Columbia University Medical Center) for the article; GalT‐KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels.

This year’s Keith Reemtsma Lectureship was awarded to David Sachs and the IXA Honorary Membership Lectureship, to Bruno Reichart.

TTS-IXA Scientific Congress Award Recipients

Awards were bestowed upon the following young investigators for the abstracts that they presented. These can be viewed by following the individual links from this page.

  • Yuichi Ariyoshi (USA)
    Localization of hCD47 expression in kidney grafts plays a key role for the development of post kidney xenotransplant proteinuria and systemic inflammatory responses through the CD47/SIRPα and/or CD47/TSP-1 pathways
  • Paolo Brenner (Germany)
    Breakthrough in orthotopic cardiac xenotransplantation (oXHTx): Completion of the preclinical life-supporting pig-to-baboon oXHTx study with first successful long-term survival (terminated on day 90 and up to 195 days) in 6 of 8 cases using CD40mAb costimulation blockade for immunosuppression 
  • Angela Chen (USA)
    Impact of genetic modification of porcine aortic endothelial and lung microvascular endothelial cells on human platelet aggregation
  • Wenlong Huang (Canada)
    Rejection of Neonatal Pig Islet Xenografts by Mouse or Human Immune Cells in NOD.SCID Gamma Mouse Model
  • Abdulkadir Isidan (USA)
    Investigation of the human immune response to porcine corneal xenografts using a bioreactor perfusion system
  • Xiaoqian Ma (China)
    Human CD27+HLADR+ Treg show xeno-antigen specific protection of porcine neonatal islet xenograft in humanized mice model
  • Raza Naqvi (USA)
    Development of a bioassay for circulating anti-SDa antibody in 3D pig-to-human in vitro perfusion model
  • Kazuhiro Takeuchi (USA)
    B4 and CMAH KO pigs may express new antigenic specificities that cause delayed vascular xenograft rejection in pig-to-baboon kidney transplantation
  • Takayuki Yamamoto (USA)
    Survival of genetically-engineered pig kidney grafts in baboons: a comparison of FDA-approved and anti-CD40mAb-based immunosuppressive regimens
  • Chang Ho Yoon (S Korea)
    Long-term survival of full thickness corneal xenografts from α1,3-galactosyltransferase gene-knockout miniature pigs in nonhuman primates
Left to Right: L. Buhler, K. Takeuchi, A. Chen, A. Isidan, R. Naqvi, Y. Ariyoshi, P. Brenner, A. Azimzadeh, W. Huang, X. Ma, T. Yamamoto, C. Ho Yoon

Congratulations to our colleagues on their well-deserved achievements!

Highlights from the Munich IXA 2019 Congress (by Peter Cowan)

The 2019 IXA Congress in Munich was an outstanding success, both scientifically and socially. The task of summarizing the scientific highlights of the Congress is not easy, for a number of reasons; it is impossible to attend all presentations, and one must attempt to avoid subconscious bias towards one’s own areas of interest. I therefore apologize in advance if I have missed your particular favorites!

One area in which the field continues to advance rapidly is genetic modification of the donor pig, and in particular the application of gene editing to generate multi-modified animals. Hinrichs et al (presentation 225.3) reported the CRISPR/Cas9-mediated introduction of the growth hormone receptor knockout (GHR-KO) mutation into GTKO/hCD46/hTBM pigs. Importantly, the GHR-KO phenotype (designed to address the problem of organ xenograft overgrowth in primate recipients) was maintained in the resulting pigs. Several presentations (115.3, 400.1, 400.3) described the use of organs from “Pig 2.0” in various preclinical models (discussed further below). Pig 2.0 contains a set of undefined modifications including deletion of carbohydrate xenoantigens and expression of complement regulators ± coagulation and immune regulators. Ayares et al (326.1) reported the production of pigs with 9 genetic modifications (triple antigen knockout + 6 human transgenes). A note of caution was sounded by Takeuchi et al (300.3), who reported the apparent generation of new antigenic targets in pigs deleted for 2 non-Gal carbohydrate xenoantigens. Clinically acceptable drug treatment remains a challenge. Yamamoto et al (225.5) reported that immunosuppression with FDA-approved drugs in a kidney xenograft preclinical model was clearly inferior to an anti-CD40-based regimen (median survival 13 days versus 186 days). Hara et al (231.11) reported that the anti-inflammatory reagent tocilizumab (anti-IL-6 receptor) may actually have detrimental effects on pig organ xenografts, because it increases IL-6 levels in recipients and does not block the pig IL-6R. One approach to reduce the immunosuppressive drug burden may be to infuse xenospecific regulatory T cells. Ma et al (301.2) showed the superior protective function of HLA-DR+ CD27+ human Tregs in humanized mice transplanted with porcine islets. Similarly, Noyan et al (231.1) reported that highly xenospecific human Tregs can be identified and isolated on the basis of their CD4+ CD154- GARP+ phenotype. Noyan et al (301.3) also developed a chimeric antigen receptor (CAR) specific for porcine SLA, and used it to generate SLA-CAR Tregs. These cells were shown to inhibit rejection of xenogeneic islets and skin in humanized mouse models.




Porcine islet quality and function are critical to the success of islet xenotransplantation. Mohammadi et al (325.2) described the positive effects of the necroptosis inhibitor Nec-1 on the maturation and function of cultured islets from young pigs. Mourad et al (325.1) reported on genetic modifications designed to improve the relatively poor insulin secretory function of porcine islets. Islet-specific expression of glucagon-like peptide 1 (GLP1) and a constitutively active type 3 muscarinic receptor (M3R) significantly enhanced insulin secretion both in vitro and in vivo.

Further progress was reported in several preclinical models. Lovasik et al (231.2) achieved long-term survival (mean 242 days) of GTKO/hCD55 kidney xenografts in rhesus macaques with low pre-transplant xenoantibody titers, treated with anti-CD4, anti-CD154, MMF and steroids. Preliminary results suggested further improvement with the addition of anti-CD20 to the protocol. Ma et al (301.2) compared kidney xenografts from Pig 2.0 and GTKO/hCD55 donors in cynomolgus monkeys. The rate and timing of rejection appeared similar in both groups, although one recipient of a Pig 2.0 kidney survived for more than 235 days. Pig 2.0 livers were also transplanted into baboons by Detelich et al (400.3). Survival in this study was 14, 8, 7, 0, 0 and 0 days. Brenner et al (115.1 and P.150) presented a summary of their ground-breaking study (published in Nature) of orthotopic pig-to-baboon cardiac xenotransplantation using GTKO/hCD46/hTBM donors, with survival up to 195 days.

The potential for viral transmission is a key concern in xenotransplantation. Krüger et al (225.4) reported on the transmission of porcine circovirus 3 (PCV3) in baboon recipients of orthotopic GTKO/hCD46/hTBM cardiac xenografts. In the 2 longest-surviving recipients (182 and 195 days), transmission of PCV3 to all organs tested was clearly demonstrated, illustrating the importance of eliminating potential viral pathogens from the donor herd.

Finally, updates on current and planned clinical trials were presented. Holzer et al (220.4) reported on an FDA-approved Phase I clinical trial in the US, in which GTKO pig skin is transplanted transiently (5 days) to patients with severe burns, followed by autografting. Preliminary results are encouraging, with good clinical outcomes and no evidence of PERV transmission. Kim et al (115.6) and Park et al (305.1) described the proposed clinical trials of corneal and islet xenotransplantation in South Korea, which are awaiting final government approval.

Please look for additional details from the Congress on the recently updated IXA website, including official recordings of presentations that are now available online to all IXA members.

IXA Member Survey Results

The results of the member survey have been compiled and IXA leadership devoted much of their strategic planning session in Munich on to how to translate member suggestions into concrete offerings.

Members identified several areas of strength, including our ability to shape the field, to push forward ethical investigation of clinical xenotransplantation, and, importantly, keeping the field active during some lean years. Free access to our journal, opportunities for training, networking opportunities and communication were all positively received.

Several areas for improvement were also identified. Broadly, these concerned opportunities and support for younger investigators including financial support and mentorships; raising funds directly to support research; updating our web presence and finding the right mix of traditional and social media to accommodate our members preferences; establishing additional meetings, symposiums or webinars on important topics to enhance our educational and networking opportunities; increasing our profile and public awareness by interactions with other sections of TTS, and engaging and educating health professionals and lay persons on the topic of xenotransplantation.

Initiatives that will allow us to better address our members’ needs have already begun. These include better use of our communication assets, (soon to come) updates to our website, and preliminary inquiries into establishing a fund to support travel expenses for young investigators. Other opportunities are still in various stages of discussion and include ways to support more meaningful mentorships; encourage young investigators; promote public awareness and support; and the feasibility of creating an endowment for research. It has also been suggested that in our role as a premiere promoter of xenotransplantation, that the IXA Council should take the lead in reviewing potential requirements necessary to proceed with eventual clinical trials.

While it may take time to accomplish everything we set out to do, it is important to recognize the value of our member’s input and the trust bestowed on our elected representatives to carry out our program on their behalf. We thank those who took the time to participate in the survey and look forward to their support as we move forward with our plans. Please feel free to send any additional comments or feedback that you might have to Suzanne Landis This email address is being protected from spambots. You need JavaScript enabled to view it.. We look forward to hearing from you.

News of interest

The creation of a special fund has been proposed to help expand the participation of young members in our scientific community by subsidizing their travel to key IXA events. Details are still being finalized. Look for more information in subsequent newsletters or the website on how you, our members, can contribute to the future of xenotransplantation by contributing to this worthwhile endeavor!

Social

Contact

Staff Directory
+1-514-874-1717, X:216
This email address is being protected from spambots. You need JavaScript enabled to view it.

Address

The Transplantation Society
International Headquarters
505 Boulevard René-Lévesque Ouest
Suite 1401
Montréal, QC, H2Z 1Y7
Canada