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Resumen
No cabe duda de que poder disponer de órganos animales para trasplante solucionaría el problema de su escasez. Para que los xenotrasplantes puedan llegar a ser una realidad clínica, se debe superar de forma consistente tres barreras: la inmunológica, la fisiológica y el riesgo de xenozoonosis. Desde el punto de vista inmunológico, la condición necesaria sería que el xenorrechazo pudiera modularse y transformarse a un allorejection-type. Los avances en la tecnología transgénica han resuelto por completo el rechazo hiperagudo, y así en los ensayos preclínicos de órganos porcinos transgénicos para proteínas reguladoras de complemento realizados hasta el momento se han obtenido sobrevidas máximas de meses para el riñón y el corazón, y de 8 días para el hígado. Estas sobrevidas han permitido estudiar la compatibilidad fisiológica de estos órganos porcinos trasplantados en los monos durante estos períodos.
En cuanto a las barreras infecciosas, con el desarrollo biotecnológico actual en el área de la producción porcina, se asegura el nacimiento de lechones completamente libres de patógenos específicos. En 1997 se demostró in vitro que retrovirus endógenos porcinos podían transfectar linfocitos humanos. Sin embargo, diversos trabajos clínicos, con tejidos u órganos perfundidos confirman la ausencia de infectividad in vivo de estos pacientes por retrovirus porcinos.
Hasta la fecha no se ha comunicado ningún xenotrasplante clínico con órganos porcinos transgénicos. La razón de ello es que existe unanimidad en que todavía las barreras inmunológicas no se han superado. En la actualidad todos los esfuerzos están orientados a estudiar los mecanismos del rechazo vascular agudo retardado para así poder diseñar estrategias que lo prevengan con efectividad.
Palabras clave:
Xenotrasplante
Xenorrechazo
Órganos transgénicos
Xenozoonosis
Supervivencia
h-DAF
The availability of animal organs for transplantation would undoubtedly solve the problem of organ scarcity. For xenotransplantations to become a clinical reality, three barriers must consistently be overcome: immunological and physiological obstacles and the risk of xenozoonosis. From the immunological point of view, the necessary condition would be that xenorejection could be adapted and transformed to the “allorejection-type”. Advances in transgenic technology have completely resolved the problem of hyperacute rejection; thus, in the preclinical trials of transgenic pig organs for complement regulatory proteins performed to date, maximum survivals of months for kidney and heart and of eight days for liver have been obtained. These survivals have enabled the physiological compatibility of these pig-to-monkey transplanted organs to be studied in these time periods.
Concerning infectious obstacles, current biotechnological development in the area of pig production guarantees the birth of piglets completely free of specific pathogens. In 1997 porcine endogenous retroviruses were demonstrated to be able to transfect human lymphocytes in vitro. However, several clinical studies, with perfused tissues or organs confirmed that these patients could not be infected in vivo by porcine retroviruses.
To date, there have been no reports of clinical xenotransplantation with transgenic pig organs because there is unanimous agreement that the immunological barriers remain to be overcome. Currently, all efforts are directed towards studying the mechanisms of acute delayed vascular rejection in order to design effective strategies for its prevention.
Key words:
Xenotransplantation
Xenorejection
Transgenic organs
Xenozoonosis
Survival
hDAF
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