LOS ANGELES — In a world-first, researchers at Children’s Hospital Los Angeles (CHLA) are investigating the use of genetically engineered pig hearts as a temporary solution—or “bridge”—for critically ill babies awaiting heart transplants. This groundbreaking preclinical research, led by congenital heart surgeon Dr. John David Cleveland, could pave the way for a life-saving alternative for infants with severe heart conditions, particularly those suffering from single-ventricle heart disease.
The CHLA team presented their latest findings at the International Society for Heart and Lung Transplantation Annual Meeting in Boston, showcasing a potential new approach for babies who have few options while waiting for a human heart. These infants often struggle to survive the wait due to complications with current support devices like ventricular assist devices (VADs), which are mechanical pumps used to circulate blood. For babies with complex heart anatomy, like single-ventricle disease, VADs can be difficult to manage, with only about 30% surviving three months on such devices due to risks like strokes and infections.
“A machine like a VAD cannot constantly adapt to the unique physiology of these infants the way a living heart can,” explained Dr. Cleveland. “Our goal is to use pig hearts to support these babies until a human heart becomes available.”
The CHLA team has spent five years conducting preclinical studies, supported by a grant from the National Institutes of Health. So far, they have transplanted genetically modified pig hearts into 14 young baboons. Eight of those baboons have survived for several months, and one has lived nearly 21 months—the longest survival ever recorded for a nonhuman primate with a pig heart transplant.
In another first, the researchers successfully replaced a pig heart with a same-species heart (an allograft) in two baboons, demonstrating that a temporary xenograft could be safely replaced with a permanent human heart in future clinical scenarios.
The pig hearts used in the study were genetically engineered to reduce the risk of rejection and came from Yucatan miniature swine, which grow more slowly and are better suited for infant-sized recipients. Advances in genetic engineering and immunosuppressive therapies, including an investigational drug called tegoprubart, are helping improve the acceptance of these foreign organs.
“This is not the same science it was in the 1980s when ‘Baby Fae’ received a baboon heart,” Cleveland said, referencing the first infant cardiac xenotransplant attempt, which ended in rejection after 21 days. “Genetic modifications and better immunosuppressive drugs have changed the landscape.”
Importantly, Dr. Cleveland noted that infants may be better candidates for xenotransplants than adults, as children under 18 have significantly fewer antibodies to pig tissues.
“The immature immune systems of babies may actually be more capable of accepting these organs than adults,” Cleveland explained. “While more research is needed, our hope is that this approach could eventually offer a better chance at life for these critically ill infants.”
The CHLA team continues to refine their methods with the goal of bringing this approach closer to clinical use, potentially offering families an alternative to long, uncertain waits for donor hearts.
