By Kaitlyn Schaeffer
Three thousand people in the United States are currently on the waiting list for a heart transplant. Unfortunately, only about 2,000 donor hearts become available every year. Those patients awaiting transplants must instead rely on machines to circulate their blood for them, devices that put them at risk for blood clots, internal bleeding, and various infections.
Dr. Muhammad M. Mohiuddin of the National Heart, Lung, and Blood Institute’s Cardiothoracic Surgery Research Program thinks xenotransplantation (the transplantation of tissues, cells, or organs across species) could provide a viable solution to the organ shortage problem: “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 revitalize progress in the xenotransplantation field.”
In a study led by Dr. Mohiuddin, piglets were genetically engineered to grow hearts that would later be transplanted into baboons. These hearts were attached to the baboons’ circulatory systems. The host baboons own hearts remained in place, however, to continue performing their regular functions.
The piglets were divided into four groups; each group received different genetic modifications.
The group of porcine hearts that performed the best had an average survival of 200 days, which is more than twice the survival rate of hearts in previous studies. The lowest performing heart stopped beating at 146 days; the best performers were still beating at the time the study was published, more than 500 days after implantation occurred.
The research group attributes the success of these hearts to two things. This group of piglets was genetically engineered to have the enzyme alpha 1-3 galactosidase transferase deactivated (eliminating one potential source of immunological rejection); this was also the only group of hearts engineered to have the human thrombomodulin gene, the expression of which prevents issues associated with clotting. Additionally, instead of relying on general immunosuppression to limit organ rejection, the researchers implemented a form of target-specific immunosuppression. No infections or other complications arose in the group of baboons that received these hearts.
“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,” Dr. Mohiuddin concluded.
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