Xenotransplantation – the Future of Transplant?

Recently, a 58-year-old man received a heart transplant using a donor heart that came from a pig.  This is only the second instance of a pig-to-human heart transplant.  Doctors at the University of Maryland Medical Center performed the surgery on September 20, 2023. 

The heart came from a genetically modified pig grown by Revivcor, a subsidiary of the United Therapeutics Corporation. The pig had 10 genes edited, including three genes that were inactivated to eliminate the alpha gal sugar in the pig’s blood cells, which can trigger a severe reaction in the human immune system, causing organ rejection. An additional pig gene was modified to control the growth of the pig’s heart while 6 human genes were added into the pig’s genome to increase acceptance by the immune system. The FDA first approved the gene edited pigs in 2020 for potential therapeutic use and consumption.

Revivicor has been experimenting with animal genes for nearly thirty years, and it is the company that cloned Dolly the Sheep in 1996.  In 2000, they cloned pigs for the first time, and in 2020 Revivicor received a first-of-its-kind approval from the FDA for use of the GalSafe™ pig as a source of food for human consumption, as well as a source of human therapeutics.  In 2021, Revivicor’s UKidney™ from a pig was transplanted into the body of a recently deceased human maintained on artificial support.

Recovering complete organs from pigs may be groundbreaking, but the first porcine heart valve was used to repair a human heart in 1965.  Pig valves have been successfully used in human hearts for over thirty years.  Hearts are harvested from freshly killed pigs under clean conditions and the porcine tissue is refrigerated right away. Under sterile conditions, the valves are removed from the pig’s heart.  The excess tissue and myocardium are then removed.  The pig valve is mounted to a stent (frame) and reinforced with Dacron cloth and sutures.  After mounting, the valve is checked under a microscope and cultures taken. 

Porcine valves usually last an average of ten years. However, some have lasted as long as seventeen years.  Generally, pig valve replacements wear out faster in younger, more active individuals.  This progressive tissue degeneration can be caused by calcification and collagen deterioration.

The use of pig hearts for transplantation is exciting, but it also raises many questions to which the answers are unknown.  Will this help reduce the wait times for organs, saving the lives of people who die while waiting for a heart transplant?  Will the same durability problems found with the valves carry over to the transplanted hearts, causing them to wear out as quickly as the valves?  What kind of anti-rejection medicines will be required, or will scientists be able to genetically modify the hearts to the point that they are accepted by the human body just like the valves currently are?

A brave new frontier in the world of transplantation is on the horizon.