Heart transplantation is the main treatment for end stage heart failure. Around 3,000 people in the US are currently on the waiting list for a heart transplant, but despite this, only 2,000 donor hearts become available each year. In the meantime, heart patients awaiting a transplant must rely on mechanical devices, which can increase the risk of infection, blood clots and bleeding in the patient.
A proposed alternative has been to use animal hearts in human patients, which is known as "xenotransplantation."
Lead investigator Dr. Muhammad M. Mohiuddin, of the National Heart, Lung, and Blood Institute's Cardiothoracic Surgery Research Program, explains the rationale behind xenotransplantation:
"Until we learn to grow organs via tissue engineering, which is unlikely in the near future, xenotransplantation seems to be a valid approach to supplement human organ availability. Despite many setbacks over the years, recent genetic and immunologic advancements have helped revitalized progress in the xenotransplantation field."
Two main problems with xenotransplantation have been overcome by Dr. Mohiuddin's team as part of this research.
Firstly, pigs were genetically engineered to be a source of donor organs. These pigs had human genes that make their organs more compatible with human physiology. Pigs were chosen because their anatomy is similar to human anatomy.
The piglets were genetically engineered to have the enzyme alpha 1-3 galactosidase transferase deactivated, which eliminates one potential cause of immunologic rejection. The piglets' hearts also expressed human transgenes to prevent blood from clotting.
Secondly, rather than employing the usual generalized immunosuppression to limit rejection of the transplanted heart, the scientists pioneered a form of target-specific immunosuppression, which is less toxic.
Piglet hearts were attached to baboons' circulatory systems to test viability
To test the survival of the genetically engineered pig hearts, the transplanted organs were attached to the circulatory systems of host baboons, in their abdomens. The baboons' own hearts remained in place and continued to provide circulatory function.
Using animal hearts - such as this pig heart - in human patients is known as "xenotransplantation."
Four groups of pig hearts in the study each received different genetic modifications.
One group of piglet hearts that had been engineered to contain a human gene had an average transplant survival of 200 days. This was much longer than the average survival times of the other three groups, which survived for 21 days, 70 days and 80 days.
Within the group that had an average survival of 200 days, two of the hearts had stopped beating 146 and 150 days after the transplant, but the other three transplanted hearts survived for 200-500 days at the time of the study's publication.
Dr. Mohiuddin believes that this group of hearts survived longer than the others because it was the only group to feature the human thrombomodulin gene. Expression of this gene prevents some of the clotting problems encountered in organ transplantation.
No infections or other complications were observed in the longest-surviving group of hearts.
The next step for the researchers is to test whether these long-lasting genetically engineered pig hearts can sustain full life support. To do this, they will replace the hearts of the baboons with the pig hearts.
Dr. Mohiuddin concludes:
"Xenotransplantation could help to compensate for the shortage of human organs available for transplant. Our study has demonstrated that by using hearts from genetically engineered pigs in combination with target-specific immunosuppression of recipient baboons, organ survival can be significantly prolonged. Based on the data from long-term surviving grafts, we are hopeful that we will be able to repeat our results in the life-supporting model. This has potential for paving the way for the use of animal organs for transplantation into humans."