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Zoonotic Diseases

The emergence of new, unrecognized pathogens in the  xenotransplant recipient is one of the primary concerns about the pig-to-human heart xenotransplantation. A major concern is the possibility of zoonotic diseases developing in the xenotransplant recipient and spreading to the public. Both in the United States and around the world, zoonotic diseases are quite widespread. According to scientists, more than 6 out of every 10 recognized infectious diseases in humans are transferred by animals. While the risk of zoonotic diseases from the donor organ may be allowable for the xenotransplant recipient, the risk of a zoonotic agent with unforeseeable pathogenicity from the xenotransplant recipient to the community at large would an inadmissible public health risk. Citation:  Boneva, R. S. (2001, January 14).  Infectious Disease Issues in Xenotransplantation.  Retrieved from National Library of Medicine:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88959/ Sawyer, B. (2016).  Zoonotic Disease
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Immunologic Rejection

Within minutes after pig-to-human heart xenotransplantation, hyper-acute rejection might occur, resulting in an acute injury to the vascular endothelial cells of the donor organ. Xenoractive antibodies and the complement system appear to be the two primary factors that mediate HAR.   Approaches that will prevent HAR include genetically modified pigs and expression of human complement regulatory proteins in the pig.   According to studies on immunologic rejection, many genetically engineered pigs were generated to overcome molecular incompatibilities. Eliminating the gene coding for the enzyme  a (1-3) will result in the absence of an  a (1-3)-Gal epitope in the pig and could significantly decrease the risk of HAR.  Pigs and humans exhibit similar human complement regulatory proteins (CRPs), but pig CRPs are not enough to protect pig cells from human complement-mediated injury. Human CRPs (hCRPs) can be introduced to pig cells to inhibit human complement-mediated injury. Researchers hav
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First Successful Pig-to-Human Heart Xenotransplant

The world’s first pig-to-human heart xenotransplant was successfully performed on January 7, 2022, at the University of Maryland School of Medicine (UMSOM) in Baltimore, Maryland. The 8-h procedure was implemented by the cardiac surgery team that was led by Dr. Muhammad Mohiuddin and Dr. Bartley Griffith. It denotes the first time a pig organ has been relocated into a human with a chance to survive and recover. David Bennett, the 57-year-old male patient with terminal heart failure, received a transplanted heart from a genetically modified pig. The heart xenotransplant was the only viable solution for various reasons. Due to his history of disobedience, he was denied five times previously for a traditional heart transplantation. David Bennett was already on cardiac support for almost two months, furthermore he couldn’t acquire a mechanical heart, because of heart arrhythmia. Figure presents the first successful pig-to-human heart xenotransplantation at (UMSOM). Citation:  Rozenbaum, M.
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Genetic Engineering

Genetic engineering of the donor is a powerful asset that will incite the success of the pig-to-human heart xenotransplantation. The transplantation of organs from wild-type (genetically unmodified) pigs into humans resulted in hyper-acute rejection. As a result, genetic engineering of the pig as an organ source is an introduced technique that will improve the survival of the relocated pig heart.    The latest xenotransplantation that was performed at the University of Maryland Center (UMMC) removed three pig genes that trigger attacks from the human immune system (Alpha-Gal, Cmah, and Beta-4-gal) and added six human genes, which included two human complement inhibitor genes (CD46 and DAF), two genes that promote normal blood coagulation (prevents blood vessel damage) (EPCR and Thrombomodulin), and two human immune-modulating genes (CD47 and HO1).   In addition, a new drug from Kiniksa Pharmaceuticals in combination with other anti-rejection drugs were used by the surgical team to help
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Overview

Xenotransplantation is the process that involves the transplantation, implantation, or infusion of nonhuman organs, tissues, or cells into a human recipient. Demand for human organs for transplantation is always higher than supply. Therefore, doctors and genetic engineers promoted the implementation of animal or nonhuman organs in xenotransplantation. Due to a severe organ shortage worldwide and other reasons, pig-to-human heart xenotransplantation is the only conceivably life-saving solution. Pigs are a promising benefactor for xenotransplantation as they share many physiological and anatomical characteristics with humans. The pig's heart undergoes ten genetic changes, in addition to a novel immunosuppressant given to the patient and a cocaine-laced solution used to breed the heart. Citation:    Heiner Niemann, B. P. (2016, January 28).  The production of multi-transgenic pigs: update and perspectives for xenotransplantation.  Retrieved from SpringerLink:   https://link.springer.c
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