2013 - IXA 2013 Congress


This page contains exclusive content for the member of the following sections: TTS, IXA. Log in to view.

IXA Symposium 2: Xeno vs Regenerative Technology

30.5 - Pancreas/ Islets - Recent progress in xenogeneic islet transplantation

Presenter: Bernhard, Hering, London, United States
Authors:

Advantages of xenoislet over alloislet transplantation

 

Bernhard J. Hering, M.D. – Schulze Diabetes institute, University of Minnesota

 

Type 1 diabetes (T1D) continues to be a major source of morbidity and mortality.  Human islet allografts restore normoglycemia and insulin independence, protect from severe hypoglycemia, and slow progression of microvascular complications in immunosuppressed type 1 diabetic recipients. These data highlight the potential of cell-based diabetes therapy.

Prolonged diabetes reversal for more than six months has now also been achieved after porcine islet xenotransplantation in non-human primates (NHP) by five groups involving the use of various tissue sources (adult, neonatal, and embryonic pig islet tissue; wild-type and transgenic), implantation sites (portal vein, omental pouch, subcutaneous tissue), immunotherapeutic protocols (immunosuppression, encapsulation), and animal models (streptozotocin-induced and surgical diabetes; cynomolgus and rhesus monkeys).

New insights suggest that the risk-benefit ratio of pig-to-human islet xenotransplants could actually be more favorable than that of human-to-human islet allotransplants. First, unlimited and on-demand availability of pig islets will boost access to islet transplants without waiting time. Second, the quality of islet products from healthy, young, living and designated pathogen-free pigs will be predictably high and not compromised - as with human islet products - by co-morbidity, brain death, age, ischemia, and disease transmission. Third, because the porcine islet amyloid polypeptide (IAPP) is considerably less amyloidogenic than human IAPP, transplanted pig islets will not be subject to IAPP-induced, non-immune-mediated graft loss. Fourth, pig islet transplants are less likely to be recognized by MHC-restricted, autoreactive, CD8+ memory T cells, thereby making posttransplant autoimmune recurrence less likely. Fifth, preemptive negative vaccination with donor antigen can be exploited to mitigate anti-xenodonor immunity. Sixth, pig islet grafts will be a treatment option for highly allosensitized patients who appear to be at no increased risk of xenosensitization compared to non-sensitized patients. Finally, genetic modification of source pigs will present opportunities for minimizing recipient immunosuppression not available to recipients of human islet allografts.

Some of the requirements for clinical translation of pig islet xenotransplantation have been met. First, the regulatory framework established by the FDA and the recommendations made by the Int’l Xenotransplant Association and the World Health Organization provide a safe and suitable framework for conducting clinical trials of investigational porcine islet products in T1D. Second, a surveillance and safety program has been developed to detect, measure, manage, report, and respond to infectious diseases caused by known infectious agents and, possibly, previously unknown or unexpected pathogens in individual recipients of pig tissues. Third, suitable, designated pathogen-free, wild-type source pigs have been generated for planned pilot clinical trials. Fourth, significant progress has been made in manufacturing clinical-grade pig islet products for use in T1D recipients. However, for clinical trials of pig islet xenotransplantation to be undertaken with high expectation of benefit, safe and effective rejection prophylaxis strategies remain to be developed in NHP that do not interfere with islet xenograft function.

 


Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Social

Contact

Staff Directory
+1-514-874-1717
info@tts.org

Address

The Transplantation Society
International Headquarters
740 Notre-Dame Ouest
Suite 1245
Montréal, QC, H3C 3X6
Canada