Clinical Trials and Projected Future of Liver Xenotransplantation

Abstract

The trial and error of the pioneering xenotransplant trials over the past three decades has defined the limitation of the species used. Success was tantalizingly close with the chimpanzee, baboon, and other primates. The use of more disparate species has been frustrated by the xenoantibody barrier. Future attempts at clinical xenotransplantation will be hampered by the consideration of the species of animals and the nature of the organs to be transplanted. On one hand, primate donors have the advantage of genetic similarity (and therefore potential compatibility) and less risk of immunologic loss. On the other hand, pig donors are more easily raised, are not sentient animals, and may be less likely to harbor transmissible disease. It is recognized that the success of xenotransplantation may very with different organs. Because it is relatively resistant to antibody-mediated rejection, the liver is the organ for which there is the greatest chance of long-term success. Consideration of using xenotransplants on a temporary basis, or as a "bridge" to permanent human transplantation, may allow clinical trials utilizing hearts or kidney xenografts. Issues on metabolic compatibility and infection risks cannot be accurately determined until routine success in clinical xenotransplantation occurs. Based on a limited experience, the conventional approaches to allotransplantation are unlikely to be successful in xenotransplantation. The avoidance of immediate xenograft destruction by hyperacute rejection, achieved using transgenic animals bearing human complement regulatory proteins or modulating the antigenic target on the donor organ, is the first step to successful xenotransplantation. The ability to achieve tolerance by establishing a state of bone marrow chimerism is the key to overcoming the long-term immunologic insults and avoiding the necessarily high doses of nonspecific immunosuppression that would otherwise be required and associated with a high risk of infectious complications. Xenotransplantation faces criticism that is strongly reminiscent of that leveled against human-to-human transplantation during the late 1960s and early 1970s. Yet with persistence, the field of human-to-human transplantation has proved highly successful. This success was the result of a stepwise increase in our understanding of the biology of rejection, improvements in drug management, and experience. It is possible that xenotransplantation may not be universally successful until further technologic advances occur; yet cautious exploration of xenotransplantation appears warranted to identify those areas that require further study.

Appropriate Donor Size for Porcine Liver Xenotransplant

“…Therefore, it might be a greater chance for long-term success of liver xenotransplant. 20,22 Another crucial questions is: Whether the pig organ is physiologically compatible with the human's environment or not, and will 1 gram of pig liver work physiologically the 23 However, 1 potential problem is that some of the protein-protein reactions between species do not function well. 24 Additionally, the life span of pigs is less than that of humans.…”

Lebertransplantation bei metabolischen Lebererkrankungen im Erwachsenenalter

“…Abgesehen von der ethischen Problematik sind viele technische Fragen noch ungelöst. Dazu gehören Unterschiede in den Stoffwechselwegen und Endprodukten der Proteinbiosynthese, ein höheres immunologisches Risiko sowie die potenzielle Übertra-gung von Zoonosen auf den Menschen [245,246].…”

Akutes Leberversagen

“…Die einzigen Xenotransplantationen beim akuten und chronischen Leberversagen wurden in den 1990er Jahren an drei Patienten durchgeführt,wobei das längs-te Überleben 70 Tage betrug [90].…”