Concluding Remarks
The xenotransplantation field is moving ahead rapidly. Many carefully designed studies have been instrumental in the elucidation of
the fundamental mechanisms involved in xenograft rejection, and the enhanced comprehension of physiological and safety issues,
resulting in the development of appropriate intervention strategies. In this light, the versatile technology of genetic engineering has
proven a powerful tool, enabling multiple transgenic modifications, designed to overcome the hurdles still associated with pig-to-
primate xenotransplantation. This has made possible the elimination of HAR by the use of transgenic pig organs expressing human
complement regulatory molecules or indeed lacking the _ Gal epitope. Ongoing refinements are aimed at the mitigation of
coagulopathy and the improvement of the safety profile of pig-to-primate xenotransplantation. These approaches, in combination
with the development of novel immunosuppression and tolerance-inducing protocols, provide hope that a strategy enabling safe,
long-term xenograft survival will be available in the not too distant future.
Nonetheless, progress in this field must meet the highest ethical and safety requirements. In addition, the risk/benefit ratio of a
potential clinical application of xenotransplantation must be carefully and stringently evaluated. In this context, the ethical principles
outlined in the position paper of the Ethics Committee of the International Xenotransplantation Association remains the cornerstone
document governing the conduct necessary for clinical trials. In addition, it is noteworthy that the development of internationally
accepted guidelines, with the aims of promoting cooperation and harmonising global practices related to xenotransplantation
procedures, is a key objective of a resolution recently adopted by the World Health Organisation. In all cases, convincing efficacy
data in non-human primate pre-clinical models is an indispensable requirement for progression to the clinic. In this light, the recent
publication by Valdes et al. in the absence of documented proof-of-concept data in non-human primates, raises the concern that the
study may not have been conducted in keeping with the above-mentioned position paper’s recommendations. Indeed, it is the
authors’ opinion, and that of many others, that only timely, well-planned, scientifically-rigorous and ethically-acceptable clinical
studies will provide the confidence that will be needed by society at large to allow this emerging field to meet its clinical potential.
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