Transplantation Beyond Species: The Present and Future of Xenotransplantation

Xenotransplantation (XTx), the transplantation of organs, tissues, or cells from animals to humans, is emerging as a promising alternative to address the increasing global demand for transplantable organs.Over the past two decades, substantial progress has been made in transplantation practices worldwide, driven by advancements in healthcare infrastructure and the expansion of organ donation programs involving both living and deceased donors.Global data show a significant rise in transplant activity in regions such as the United States, Europe, China, and India, emphasizing a broader international effort to address organ shortages.Despite global advances in transplantation, considerable disparities in access persist, particularly in low-and middle-income countries, where limited infrastructure and socioeconomic inequalities continue to impede equitable care.Consequently, millions of patients continue to face barriers to life-saving transplants, highlighting the urgent need for international collaboration and strategic investments to expand access.Brazil is recognized for maintaining one of the largest public transplant systems in the world.From preoperative preparation to lifelong posttransplant pharmacotherapy, transplantation constitutes one of the most resource-intensive interventions funded by the Unified Health System (Sistema nico de Sade), which accounts for approximately 96% of all heart transplants performed in Brazil. 1 Despite significant advances in transplant techniques and public policies, the supply of organs still fails to meet the growing demand, resulting in increasingly long waiting lists, as evidenced by the Brazilian Transplant Registry. 2This scenario underscores the urgent need to guarantee fair access to transplantation, as established by the 1988 Federal Constitution and Law No. 8,080/1990, 3which defines health as a right of all and a duty of the State.In the context of a shortage of human organs and increasing demand for new therapeutic alternatives, XTx has emerged as a promising and potentially viable solution.The history of XTx closely follows the overall development of transplantation.The earliest reports of such procedures involve tissue and cell transplants, rather than organ transplants. 4nitial experiments date back to the 17 th century, most notably the xenotransfusions conducted by Jean-Baptiste Denis in 1667 using the blood of a lamb. 5Another significant milestone occurred in 1838, when Richard Sharp Kissam performed the first corneal XTx by transplanting porcine corneal tissue into a human patient. 6Throughout the 19 th and 20 th centuries, advances in vascular anastomosis techniques-pioneered by Mathieu Jaboulay and Alexis Carrel-enabled a series of experimental attempts that involved organs from several species, including nonhuman primates (NHP; baboons and chimpanzees), pigs, rabbits, and sheep.However, these experiments were largely unsuccessful, primarily due to the occurrence of hyperacute rejection and other severe immunological complications. 4,7e advent of modern immunosuppression in the 1960s, fueled by the discoveries of Peter Medawar and the introduction of drugs such as 6-mercaptopurine, marked a new era, enabling significant progress in both allotransplantation and XTx. 4 From that point forward, the first clinical reports of cardiac XTx in humans began to emerge.Among the key milestones: 1964 -chimpanzee heart, by James Hardy, in Jackson (USA), with a survival time of 90 min; 8 1968 -porcine heart, by Donald Ross, in London (UK), with a survival time of 4 min; 9 1968 -sheep heart, by I