H-10 : criteria for living donor transplantation
H-01 : HLA SYSTEM
Kidney xenotransplantation
Peter J Cowan1,2, David K C Cooper3 and Anthony J F d'Apice1,2
Kidney International (2014) 85, 265–275
1. Immunology Research Centre, St Vincent’s Hospital, Melbourne, Victoria, Australia
2. Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
3. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, USA
Correspondence: Peter J. Cowan, Immunology Research Centre, St Vincent’s Hospital, PO
Box 2900, Fitzroy, Melbourne, Victoria 3065, Australia. E-mail: peter.cowan@svhm.org.au
ABSTRACT
Xenotransplantation using pigs as donors offers the possibility of eliminating the chronic
shortage of donor kidneys, but there are several obstacles to be overcome before this goal
can be achieved. Preclinical studies have shown that, while porcine renal xenografts are
broadly compatible physiologically, they provoke a complex rejection process involving
preformed and elicited antibodies, heightened innate immune cell reactivity, dysregulated
coagulation, and a strong T cell–mediated adaptive response. Furthermore, the susceptibility
of the xenograft to proinflammatory and procoagulant stimuli is probably increased by crossspecies molecular defects in regulatory pathways. To balance these disadvantages,
xenotransplantation has at its disposal a unique tool to address particular rejection
mechanisms and incompatibilities: genetic modification of the donor. This review focuses on
the pathophysiology of porcine renal xenograft rejection, and on the significant genetic,
pharmacological, and technical progress that has been made to prolong xenograft survival.
Keywords: genetically modified; immunosuppression; pig-to-primate model; tolerance;
transgenesis; xenotransplantation
COMMENTS
More than a scientific curiosity ?
Xenotransplantation using pigs as donors has been studied for several decades, and porcine
cellular xenografts have already reached the stage of clinical trials.The pig is the animal
donor of choice for a number of reasons, including relatively similar organ size and
physiology, high reproductive capacity, and the potential for genetic modification to prevent
rejection and correct molecular incompatibilities.
Preclinical studies indicate that pig kidney xenotransplantation is feasible, with renal
xenografts supporting life for several weeks or months in non-human primate recipients.
However, despite considerable progress in recent years, the immunological and
pathophysiological barriers have not been completely overcome. The major challenge is to
place renal xenografts on at least an equal footing with allografts, that is, with comparable
survival rates under similar levels of immunosuppression. This is likely to require a
combination of ‘humanized’ donors and clinically applicable immunosuppressive protocols.
Herein, arel reviewed the mechanisms of porcine renal xenograft rejection and described
recent progress in moving kidney xenotransplantation to the clinic
An other major limitation to the use of xenotransplantation even with the best ‘humanized’
kidney, is the viral burden of the pig, the human pathogenicity of which is totally unknown. It
could be very dangerous to overcome natural species barriers.
Pr. Jacques CHANARD
Professor of Nephrology