A major problem hurdle in organ transplantation is a lack of healthy donors. For many years, scientists in the field of regenerative medicine have been trying to find new ways to create organs for transplant. Animals may be one source of new organs; pig hearts, for example, have long been studied as an option.
A new review in Circulation has outlined genetic and pharmacological advancements that are getting us closer to making this a reality. The work described recent experiments by German scientists in which pig hearts were successfully transplanted into baboons. This process, transplanting a heart from one species to another, is called cardiac xenotransplantation; it could be a major breakthrough for patients that will die without a new heart. It's estimated that a person with severe heart failure or other condition requiring a transplant will wait over six months before they may get a new heart, and for many, that wait is too long.
A major challenge in cardiac xenotransplantation has been immune rejection; primates, and probably humans as well, reject pig hearts; the immune system sees them as foreign and attacks them, rendering them useless in transplantation. Genetic engineering has now been used to create pig hearts that don't carry the same molecules that tend to trigger these immune rejections.
Genetic engineering has also solved a problem of incompatibility, in which proteins found in human blood and the lining of blood vessels in pig hearts trigger blood clots when combined. Researchers have also worked to create pig hearts that can produce a human protein called thrombomodulin that helps control clotting.
There have also been pharmacological solutions to hurdles in cardiac xenotransplantation. Transplant recipients, for example, often take drugs to prevent an organ's rejection by the immune system. "But those drugs don't work when you put a pig organ into a baboon," said lead study author Richard N. Pierson III, M.D., an investigator in the Massachusetts General Hospital (MGH) Division of Cardiac Surgery.
Pierson worked with collaborators to create monoclonal antibodies that can interfere with 'co-stimulatory' molecules called CD40 and CD154. These monoclonal antibodies are better than typical immunosuppressants at preventing immune cells in humans or baboons from attacking pig organs.
The review also assessed whether this entire approach could pose a risk in terms of zoonotic disease - infectious diseases that might be capable of jumping from pigs to humans. "That looks quite unlikely," said Pierson. "The culmination of a lot of research and hard work by our group and others over the last 35 years is that it now looks as though pig-to-human heart transplantation is feasible."
Pierson suggested that humans may be receiving pig heart transplants by the end of 2021.
Sources: AAAS/Eurekalert! via Massachusetts General Hospital, Circulation
