“Columbia will do it.”
It’s more than a saying—it’s a commitment to taking on challenges others shy away from. An ethos that drives innovation, compassion, and bold new approaches to patient care, especially for those facing the most complex conditions.
One such challenge lies in improving access to life-saving heart transplants for neonates with severe heart disease. Pioneering efforts at Columbia aim to bridge this critical gap, exploring cutting-edge solutions like xenotransplantation—transplants using donor hearts from genetically modified pigs.
This is more than just a novelty. There is a massive clinical need for pediatric heart transplants, and supply of baby-sized hearts is understandably extremely limited. Data from the Organ Procurement & Transplant Network from 2021 showed that 1,146 patients 17 years old or younger were on the waiting list for a heart transplant. Sadly, infants have the highest waiting list mortality rates.
Andrew Goldstone, MD, PhD, a pediatric heart surgeon, and Megan Sykes, MD, director of CCTI, have set their sights on bringing pediatric cardiac xenotransplantation to Columbia by combining research and practical applications that could save babies’ lives.
Where does the field stand now? There’s quite a bit of research that still needs to be done to verify the safety, validity, and ethicality of pediatric cardiac xenotransplantation. But in the past few years, significant progress has been made in xenotransplantation, from the world’s first successful pig-to-human heart transplantation in 2022 to the world’s second successful pig-to-human kidney transplantation in the spring of 2024. With every operation, the world’s scientists learn more about how human bodies respond to xenotransplantation and how to improve future attempts. Dr. Sykes’s lab has played a significant role by leading immunological studies of the second pig to human kidney transplantation.
In recent studies involving the transplantation of pig hearts into nonhuman primates, those pig hearts were genetically edited to lower the risk of rejection by the recipient. “Pigs are an ideal source of substitute organs because of their size, availability, breeding characteristics, and physiologic similarities to humans,” explains Dr. Goldstone. “But pigs are evolutionarily distant from primates. Therefore, pig organs are immediately rejected if transplanted into humans due to high levels of natural antibodies.”
There are a number of tools to tackle that problem. “One of the key elements that we have here at Columbia is a very unique line of pigs that were brought here by Dr. Sachs [immunologist] when he joined Columbia in 2015,” says Dr. Sykes. “We have genetically modified them in specific ways for xenotransplantation, and we're continuing to work on new genetic modifications to enhance their ability to induce tolerance and be xenograft donors.”
The pediatric heart transplant working group of CTI is also researching other ways to improve the recipient’s acceptance of a donor organ, like including tissue from the thymus gland in the transplant and using certain kinds of stem cells and bone marrow from the donor. These measures can encourage the recipient’s immune system to recognize the donor organ as part of the “self,” reducing the need for immunosuppressive treatments that can be harmful to the recipient in the long term.
Dr. Sykes also points to our unique approach of bringing researchers and clinicians into close, collaborative relationships. “We have an environment that allows surgeon-scientists to do these large animal studies and research the immunology,” she says. “The clinical team recognizes the importance of training these people and giving them protected time to do serious research, and the two groups participate together in the clinical trial meetings and human transplant immunology groups.”
A long-term goal of this work is to leverage that collaborative, multidisciplinary environment to train a new generation of transplant experts ready to take on other pressing needs in medicine, like pediatric liver transplants. It’s not just hearts; the same supply issues exist for any tiny organ a child may need to be transplanted.
We’re optimistic and excited about our progress in xenotransplantation as we strive to improve our most vulnerable patients’ lives and trajectories. There’s some evidence that younger immune systems may be trained more effectively to accept donated organs, and Dr. Sykes’ and Dr. Goldstone’s team recently received a significant grant from the American Heart Association to continue their research.
The breadth of progress is wide. A team that has completed more pediatric heart transplants than anyone else, we’re primed to break new ground that could finally address the pediatric organ supply issue in the long term. “Xenotransplantation is a field that is just getting into the clinic,” says Dr. Sykes. “I feel like the work that we've done on this for 30 years is really starting to pay off.”
Related:
- How Close Is Xenotransplantation, Really?
- History of Medicine: Columbia's First Pediatric Heart Transplant
- State of the Union: Pediatric Heart Surgery Today