Skin xenotransplantation: Historical review and clinical potential

Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Pig skin xenografts may provide temporary coverage. However, preformed xenoreactive antibodies in the human recipient activate complement, and thus result in rapid rejection of the graft. Because burn patients usually have some degree of immune dysfunction and are therefore at increased risk of infection, immunosuppressive therapy is undesirable. Genetic engineering of the pig has increased the survival of pig heart, kidney, islet, and corneal grafts in immunosuppressed non-human primates from minutes to months or occasionally years. We summarize the current status of research into skin xenotransplantation for burns, with special emphasis on developments in genetic engineering of pigs to protect the graft from immunological injury. A genetically-engineered pig skin graft now survives as long as an allograft and, importantly, rejection of a skin xenograft is not detrimental to a subsequent allograft. Nevertheless, currently, systemic immunosuppressive therapy would still be required to inhibit a cellular response, and so we discuss what further genetic manipulations could be carried out to inhibit the cellular response.