https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)61091-X.pdf

Clinical xenotransplantation: the next medical revolution?

Cross-species transplantation (xenotransplantation) offers the prospect of an unlimited supply of organs and cells for clinical transplantation, thus resolving the critical shortage of human tissues that currently prohibits a majority of patients on the waiting list from receiving transplants. Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into aged men whose "zest for life" was deteriorating, believing that the hormones produced by the testis would rejuvenate his patients. Following the pioneering surgical work of Carrel, who developed the technique of blood vessel anastomosis, numerous attempts at nonhuman primate organ transplantation in patients were carried out in the 20th century. In 1963-1964, when human organs were not available and chronic dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992, he obtained patient survival for 70 days following a baboon liver transplant. With the advent of genetic engineering and cloning technologies, pigs are currently available with a number of different manipulations that protect their tissues from the human immune response, resulting in increasing pig graft survival in nonhuman primate models. Genetically modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant.

/pdf/a-brief-history-of-cross-species-organ-transplantation-1n4cr9fgbi.pdf

A brief history of cross-species organ transplantation

Pigs as a source of grafts for xenotransplantation can help to overcome the rapidly growing shortage of human donors However, in the case of pig-to-human transplantation, the antibody-xenoantigen complexes lead to the complement activation and immediate hyperacute rejection Methods eliminating hyperacute rejection (HAR) include α1,3-galactosyltransferase (GGTA1) inactivation, regulation of the complement system and modification of the oligosaccharide structure of surface proteins The humoral immune response control and reduction of the risk of coagulation disorders are the priority tasks in attempts to overcome acute humoral xenograft rejection that may occur after the elimination of HAR The primary targets for research are connected with the identification of obstacles and development of strategies to tackle them Because of the magnitude of factors involved in the immune, genetic engineers face a serious problem of producing multitransgenic animals in the shortest possible time

https://link.springer.com/content/pdf/10.1007%2Fs13353-014-0261-6.pdf

The current state of xenotransplantation

The shortage of donor resources has greatly limited the application of clinical xenotransplantation. As such, genetically engineered pigs are expected to be an ideal organ source for xenotransplantation. Most current studies mainly focus on genetically modifying organs or tissues from donor pigs to reduce or prevent attack by the human immune system. Another potential organ source is interspecies chimeras. In this paper, we reviewed the progress of the genetically engineered pigs from the view of immunologic barriers and strategies, and discussed the possibility and challenges of the interspecies chimeras.

Genetically engineered pigs for xenotransplantation: Hopes and challenges

a Transregio Collaborative Research Center 127, Ludwig-Maximilians University, Munich, Germany b Department of Cardiovascular Surgery, Ludwig-Maximilians University, Munich, Germany c Revivicor, Blacksburg, VA, USA d Living Cell Technologies, Auckland, New Zealand e Chair of Livestock Biotechnology, Weihenstephan, Technical University, Munich, Germany f Department of Anaesthesiology and Intensive Medicine, Ludwig-Maximilians University, Munich, Germany

/pdf/discordant-cardiac-xenotransplantation-broadening-the-2s74laedhx.pdf

Discordant cardiac xenotransplantation: broadening the horizons.

Longterm clinical recovery in parkinsonian monkey recipients of ctla4-ig transgenic porcine neural precursors: 3288

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Longterm clinical recovery in parkinsonian monkey recipients of ctla4-ig transgenic porcine neural precursors: 3288