In a pioneering medical case that could help reshape the future of organ transplantation, University of Maryland researchers have released detailed findings from their second pig-to-human heart transplant, revealing both promising advances and crucial challenges that need to be overcome before the procedure can become widely available.
The study, published today in Nature Medicine, documents how Lawrence Faucette, 58, lived for 40 days with a genetically modified pig heart before the organ began failing due to immune rejection. Despite the setback, researchers say the case provided vital insights that could help prevent rejection in future transplants.
“We have taken another important step forward in the quest to address the global shortage of donor hearts, and we once again found that the porcine heart demonstrated excellent systolic and diastolic function during the initial weeks post-transplantation,” said Dr. Bartley P. Griffith, who performed both of the world’s first pig heart transplants at the University of Maryland Medical Center.
Unlike the first transplant patient in 2022, Faucette started from a stronger medical position and showed no signs of porcine virus infection, which had complicated the first case. However, despite careful screening that showed Faucette had low levels of antibodies against pig tissues, his immune system mounted an unexpected response that ultimately led to organ rejection.
The transplant initially functioned well, with the heart showing excellent performance during the first several weeks. Faucette was able to participate in physical therapy and even pedal a modified stationary bike 23 days after the surgery. However, around day 29, his condition began deteriorating rapidly.
Dr. Muhammad M. Mohiuddin, Scientific Director of the Cardiac Xenotransplantation Program, expressed both humility and determination in light of the findings. “Their sacrifice yielded crucial scientific insights into how we and others should proceed to learn how to prevent graft failure from happening in future transplants,” he said.
The research team identified several key areas for improvement in future transplants, including the need for more aggressive suppression of antibodies that can attack the pig heart. They also found that using certain blood products during the procedure may have inadvertently introduced additional antibodies that contributed to rejection.
The case represents a significant step forward in xenotransplantation – the transplanting of animal organs into humans. The pig heart used in the procedure had been genetically modified with 10 genetic changes designed to make it more compatible with the human immune system and prevent rejection.
“Despite setbacks related to immunological rejection after a few weeks, xenotransplantation and living related organ donation remain our most viable pathways forward towards sustainable organ availability to meet the needs of our aging populations,” said Dr. Mark T. Gladwin, Dean of the University of Maryland School of Medicine.
For Faucette, who was not eligible for a traditional human heart transplant due to pre-existing vascular disease and complications with internal bleeding, the experimental procedure represented his only chance at survival. When the transplanted heart began to fail after 31 days, requiring mechanical support, he chose to transition to comfort care rather than continue additional interventions.
The detailed analysis of his case revealed that the pig heart had nearly doubled in size by the time of his death, growing from 273 grams to 480 grams. Microscopic examination showed evidence of immune system attack on the heart’s blood vessels, leading to tissue damage despite the absence of significant inflammation that would typically indicate rejection.
The research team is now working on several modifications to their approach, including starting anti-rejection medications earlier, more carefully screening blood products used during surgery, and potentially adding additional genetic modifications to the pig hearts to better protect them from the human immune system.
Dr. Christine Lau, Chair of the Department of Surgery, emphasized the broader implications: “We continue to learn so much from these pioneering surgeries, and we are grateful to United Therapeutics for their support of our work as we help move the field of xenotransplantation closer to becoming a clinical reality.”
With more than 110,000 Americans currently waiting for organ transplants, the potential impact of successfully developing animal-to-human transplantation could be transformative. The insights gained from Faucette’s case bring researchers one step closer to making this possibility a reality.
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