What are xenograft models?

The term xenograft refers to a transplant of an organ or tissue from a donor that comes from a different species than the recipient. It is possible to engraft human and other species’ cells and tissues into immune-deficient models, especially from cancer cells. 

A wide range of medically relevant research has been conducted using the laboratory rat, one of the most extensively studied mammals. The popularity of this species is attributed to such characteristics as size, fecundity, behavior, ease of surgical techniques, tissue sampling, and general laboratory management.

Successful examples of xenotransplantation:

• Non-human heart to a human:

In 1984, Baby Fae, an American infant with hypoplastic left heart syndrome, became the first infant to receive a baboon heart transplant. Loma Linda University Medical Center in Loma Linda, California, performed the procedure under the direction of Leonard Lee Bailey. He died 21 days later owing to a humoral-based graft rejection mainly caused by ABO blood type mismatch, considered unavoidable due to the rarity of type O baboons. 

 It was intended to be a temporary graft, but a suitable allograft replacement was not found in time. Despite not advancing the field of Xenotransplantation, the procedure revealed the lack of organs for infants. There was a dramatic improvement in the crisis of infant organ shortages due to the story. 

A genetically modified pig’s heart was transplanted in January 2022 to a terminally ill patient, David Bennett Sr., who was ineligible for a standard human heart transplant. The pig was edited to remove enzymes that produce the sugar antigens associated with human hyperacute organ rejection. Using compassionate use criteria, the US medical regulator approved the procedure. After two months of transplantation, the recipient died. 

• Skin xenotransplantation:

Animal and human skin grafts became relatively popular in the 19th century. A pedicle skin graft or a free skin graft was used for the xenograft. Various types of skin grafts were used for the graft, including pedicle and free skin grafts. 

 It was difficult to perform pedicle grafts because the donor, for example, a sheep, had to be strapped immobile to the recipient for several days until it became vascularized. The graft could become disconnected from the donor if this occurs. Although some “successes” were reported, it is almost certain that none of these grafts were successful. 

Although many species used as donors had hair, feathers, or fur growing from the skin, the surgeons did not appear concerned. The trend was to use animals with no hair, feathers, or fur. In some cases, grafts made from frogs, sometimes “skinned alive,” may have proved successful by protecting for several days while the wound healed. Most likely, none of the grafts were permanent. 

Xenotransplantation and Ethics 

Researchers studying Xenotransplantation at the beginning of the 20th century viewed animals as a “natural” alternative to allografts, and few questioned their morality. Although some plays mocked Xenografters like Serge Voronoff and some images showed emotionally distraught primates – whose testicles Voronoff had removed – no genuine attempts had been made to question the science. The first half of the 20th century saw little interest in Xenotransplantation, at least in France. 

In 1984, animal rights activists began protesting after the Baby Fae incident, gaining media attention and demonstrating that some people believed it was unethical to use an animal’s organs to prolong a sick human’s life. By treating animals like mere tools for slaughter on demand, humans would create a world they do not want. 

Many supporters of the transplant argued that saving a human life justified the sacrifice of an animal. Animal rights activists consider Primate organs more reprehensible than pigs’ organs. Several primates exhibit stronger social structures, communication skills, and affection than mentally deficient humans and human infants, according to Peter Singer et al. Despite this, Xenotransplantation is unlikely to be prohibited by regulators due to animal suffering.  

Read more: Mouse transfection