Researchers successfully transplanted two genetically engineered heart pigs into recently deceased humans in June and July 2022, marking the most recent advancement in addressing the nationwide organ shortage for individuals with life-threatening heart diseases.
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Background
Lakhs of individuals with fatal diseases continue to be on the waitlist for organ transplantation since organ demand is much higher than organ supply. Successful xenotransplants could provide hope for critically ill patients with organ failures to increase survival and decrease associated mortality. However, the risk-benefit ratio of xenotransplantation must be ascertained, and appropriate measures must be taken to prevent organ rejections and increase the success rate of such life-saving procedures.
About the study
The transplant surgeries in the present study were performed on 16 June 2022, and 6 July 2022 at New York University (NYU) Langone Health's Tisch Hospital, and both concluded three days later. The investigational procedure was led by Nader Moazami, MD, surgical director of heart transplantation at the NYU Langone Transplant Institute. Dr. Moazami led the transplantation surgeries as a part of a larger study.
Pig hearts genetically engineered by Revivicor, Inc. (a subsidiary of United Therapeutics Corporation) were transplanted into deceased donor individuals receiving mechanical ventilation. There were no signs of rejection in the organs, and the transplanted pig hearts demonstrated normal heart functioning without ventilator requirements.
Dr. Montgomery has been a pioneer in laparoscopic kidney procurement for live organ donation and has developed domino paired renal donations, in which ≥2 recipients and donors are paired for swapping kidneys. According to him, porcine virus monitoring is a key aspect of successful xenotransplantation, which was incorporated in the present study by monitoring for the porcine cytomegalovirus (pCMV) and porcine endogenous retrovirus (PERV).
The pig's hearts chosen for transplantation were genetically modified by knocking out or eliminating four porcine genes to prevent transplant rejection and knocking in six human transgenes to promote the expression of proteins necessary for the regulation of biological mechanisms, which can be disrupted due to incompatibility between humans and pigs.
The present study provides an example of successful heart transplantation from a nonhuman organ into a human being with normal functioning without the need for additional devices to overcome organ shortage and save the lives of organ failure patients. Importantly, such studies require suitable human recipients, and the authors are thankful to the recently deceased whole-body donor and his family for the willingness to participate in such a breakthrough study. The availability of deceased donors would enable research advancements in organ transplantation, a field that has tested only animals for decades until the previous year.
About xenotransplantation
Xenotransplantation (xenos- Greek word meaning strange or foreign) refers to a heterologous transplant from one species to another. The transfer of either live cells, tissues, or organs from an animal source or human body cells, fluids, tissues, or organs with previous ex vivo contact with live animal cells, tissues, or organs to a human being is an example of a xenotransplant.
The animal organ is usually genetically modified with human gene insertions to trick the recipient's immune system into recognizing the (foreign) transplant as a tissue of the self. Recent studies have indicated that transplantation may provide therapeutic benefits for individuals with diabetes, hepatic failure, Parkinson's disease, and cancer.
The first xenotransplantation attempt was reported in 1905, in which a child with chronic renal disease received a rabbit kidney transplant. Successive studies involved renal transplants from chimpanzees to humans and heart transplants from baboons to an infant with hypoplastic left heart syndrome. Further, non-genetically engineered pig's kidneys, heart, and lungs were transplanted into a human in 1996.
On September 25, 2021, genetically engineered pig kidneys were first transplanted into a deceased human at NYU Langone Health without any signs of organ rejection and normal kidney function. For the procedure, the alpha-gal glycan responsible for the rejection of porcine tissues by human beings and the thymus gland responsible for immune recognition was eliminated from the donor pig. The procedure concluded in 54 hours after monitoring for kidney function and organ rejection. The following year, a team of doctors led by Bartley Griffith at the University of Maryland medical center transplanted a genetically engineered pig heart into an individual with a terminal illness.
Such breakthrough advancements could potentially lead to an unlimited organ supply and revolutionize transplantation research by saving the lives of terminally ill individuals. However, transplantation barriers such as hyperacute rejections, acute vascular rejections, cellular rejections, dysregulated coagulation, xenozoonosis, and immunological barriers must be addressed. The latest xenotransplantation milestone is not the end but the beginning of a longer process envisioned to overcome organ shortage and save many lives across the globe.
Sources:
- Successful Heart Xenotransplant Experiments at NYU Langone Set Protocol for Pig-to-Human Organ Transplants (2022). Available at: https://nyulangone.org/news/successful-heart-xenotransplant-experiments-nyu-langone-set-protocol-pig-human-organ-transplants (Accessed: 14 July 2022).
- Progress in Xenotransplantation Opens Door to New Supply of Critically Needed Organs (2022). Available at: https://nyulangone.org/news/progress-xenotransplantation-opens-door-new-supply-critically-needed-organs (Accessed: 14 July 2022).
- Xenotransplantation - Wikipedia (2022). Available at: https://en.wikipedia.org/wiki/Xenotransplantation (Accessed: 14 July 2022).
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