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Update: cardiac xenotransplantation Ekser B; Cooper DKCurr Opin Organ Transplant 2008[Oct]; 13 (5): 531-5PURPOSE OF REVIEW: To review the latest development in cardiac xenotransplantation in small and large animal models and related in-vitro studies. RECENT FINDINGS: With the recent introduction of alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig organs for xenotransplantation, improved cardiac graft survival has been obtained. However, this experience has demonstrated the importance of pig antigens other than Galalpha1,3Gal (Gal) antigens (so-called nonGal antigens) as targets for primate anti-pig antibodies. Several in-vitro studies have confirmed that, although the incidence and levels of anti-nonGal antibodies in nonhuman primates and humans are significantly less when compared with total anti-pig antibodies (i.e., anti-Gal + anti-nonGal), they can result in complement-mediated lysis of GT-KO pig cells. More recently, it has been demonstrated that regulatory T cells suppress the cellular xenogeneic response, thus potentially preventing or reducing T-cell-mediated rejection. The importance of thrombotic microangiopathy as a feature of the immune/inflammatory response and incompatibilities between the coagulation-anticoagulation systems of pig and primate are receiving increasing attention. Development of GT-KO pigs transgenic for one or more 'antithrombotic' genes, for example, CD39 or tissue factor pathway inhibitor, may contribute to overcoming these problems. SUMMARY: Although GT-KO pigs have provided an advance over wild-type pigs as a source of organs for transplantation into primates, further genetic modification of GT-KO pigs is required to overcome the remaining immune barriers before a clinical trial of cardiac xenotransplantation can be contemplated.|*Heart Transplantation[MESH]|*Transplantation, Heterologous[MESH]|Animals[MESH]|Animals, Genetically Modified[MESH]|Antibodies/blood[MESH]|Blood Coagulation[MESH]|Cell Transplantation[MESH]|Complement Activation[MESH]|Galactosyltransferases/deficiency/genetics[MESH]|Gene Knockout Techniques[MESH]|Graft Rejection/blood/immunology/*prevention & control[MESH]|Graft Survival[MESH]|Humans[MESH]|Swine[MESH]|T-Lymphocytes, Regulatory/immunology[MESH] |
