Xenograft rejection: Molecular mechanisms and therapeutic prospects

The use of animal organs for transplantation in humans is seen as a potential solution to the short supply of human donor organs available for clinical transplantation. However, while several attempts at clinical xenografting have been made over the last ninety years, xenotransplantation has not matched the success of allotransplantation, because of a vigorous rejection response. Xenograft rejection is mediated by mechanisms that differ from those involved in alloreactivity and which are inadequately controlled by conventional immunosuppressive agents. Xenotransplantation therefore requires the development of specific strategies to overcome rejection, through modification of the host immunity or production of genetically engineered pig organs. This article reviews the cellular and molecular events underlying xenograft rejection and the potential strategies of prevention and gives a brief history of the main attempts at clinical xenotransplantation since the beginning of the century.