New concepts of immune modulation in xenotransplantation

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The shortage of human organs for transplantation has focused research on the possibility of transplanting pig organs into humans. Many factors contribute to the failure of a pig organ graft in a primate. A rapid innate immune response (natural anti-pig antibody, complement activation, and an innate cellular response; e.g., neutrophils, monocytes, macrophages, and natural killer cells) is followed by an adaptive immune response, although T-cell infiltration of the graft has rarely been reported. Other factors (e.g., coagulation dysregulation and inflammation) appear to play a significantly greater role than in allotransplantation. The immune responses to a pig xenograft cannot therefore be controlled simply by suppression of T-cell activity. Before xenotransplantation can be introduced successfully into the clinic, the problems of the innate, coagulopathic, and inflammatory responses will have to be overcome, most likely by the transplantation of organs from genetically engineered pigs. Many of the genetic manipulations aimed at protecting against these responses also reduce the adaptive response. The T-cell and elicited antibody responses can be prevented by the biological and/or pharmacologic agents currently available, in particular, by costimulation blockade-based regimens. The exogenous immunosuppressive regimen may be significantly reduced by the presence of a graft from a

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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