Pig Hearts in Nonhuman Primates: A Success Story
Transplant researchers from Mayo Clinic transplant scientists have made tremendous progress such progress against immune system rejection in transplants and now they are reporting the longest median survival of 96 days of pig hearts transplanted into nonhuman primates using an experimental method known as "heterotopic" transplantation. This technique is a significant advancement toward use of tissues and organs from specially bred animals to ease the worldwide shortage of organs for humans whose survival depends on a heart transplant. This report was published in recent edition of the Journal of Thoracic & Cardiovascular Surgery.
The heterotopic approach that was tested by the Mayo group involves grafting pig hearts in the abdomens of seven nonhuman primates. A heterotopic transplant does not require the grafted heart to perform life support. Instead, heterotopic transplants test methods to control and prevent rejection by the recipients' immune systems.
Mayo Sets New Survival Record
By establishing the 96-day median survival, the Mayo Clinic group has set a new survival record for this kind of preclinical xenotransplantation (interspecies transplantation). This success sets the stage for the next step: obtaining long-term survival with transplanted animal hearts that are required to support the life of the recipient animal. In July, the Mayo transplant team's expertise in this area was acknowledged by the award of a $4.5 million grant for xenotransplantation research from the National Institutes of Health.
"The work represents continued progress in the field of cardiac xenotransplantation so that clinical application is now much closer," notes Christopher McGregor, M.B., F.R.C.S., lead surgeon of the Mayo Clinic xenotransplantation team. Mayo scientists say that it will take several more years of improvements and experience with the next phase of research before cardiac xenotransplantation becomes clinically available. The current results must be duplicated in the life-supporting orthotopic transplant model in which the animal organ not only is accepted, but functions fully and effectively.
Significance of the Mayo Clinic Research
Achieving prolonged xenograft median survival has been the goal of major transplant centers around the world as a way to meet the growing demand for donor organs. Worldwide, there is a drastic shortage of organs available for lifesaving heart, liver and kidney transplants. An estimated 40,000 people in the United States suffer from congestive heart failure annually and could benefit from a heart transplant. Yet only 2,500 heart transplants are performed due to lack of suitable donor organs. This situation is expected to continue as such organ-destroying conditions as heart disease and hepatitis C/liver disease reach epidemic proportions in some areas of the world. Transplant biology specialists at Mayo Clinic and elsewhere are working on a number of strategies to alleviate this looming public health crisis: xenotransplantation, organ regeneration, organ repair, advanced artificial organs and improved organ transplantation techniques.
About the Experiment
The immune barriers to successful xenotransplantation include hyperacute rejection and acute vascular rejection. Both result in destruction of a transplanted organ by the donor's immune system. In the current experiment, the Mayo team was able to control rejection through the use of genetically modified pigs that are specially bred to be organ donors and by using antirejection drugs. As a result, the donor hearts are compatible with the recipients' complement regulatory system, a component of the immune system. The grafted organs survived 15 to 137 days. Only two grafts were lost due to rejection. Says Dr. McGregor, "The next step is to explore life-supporting xenografts. If the results from this current experiment can be duplicated in the orthotopic position, we are on the threshold of clinical application of cardiac xenotransplantation."
More information on this topic and many other exciting research occurring at Mayo clinic can be found at the their website.