Xenotransplantation: facts and fiction

Xenotransplantation will certainly solve the problem of the allogeneic organ shortage if long-term organ function can be achieved. Acceptance or rejection of the grafts depends not only on immunological mechanisms but, as already recognized in chronic rejection (i.e. transplant atherosclerosis), on many other biochemical, physiological, and even morphological characteristics including inflammatory events originating from infections. The way in which signals in the form of hormones, neurotransmitters, enzymes and growth factors are translated in xenogeneic systems has not received adequate attention, if any at all. Central questions still to be answered are: How many xenogeneic hormonal and enzymatical interactions are possible? Are they able to maintain the metabolism in a foreign organ or body and for how long? In addition, transport molecules, the most important of which is albumin, must be considered when trying to achieve long-term survival time using organs from a widely divergent species. Large quantities of foreign proteins, mediators and enzymes are released into the circulation when, for example, xenogeneic livers or other organs suffer from HXAR. The function of the liberated enzymes, hormones and inhibitors is far from being understood or even investigated. The amount of potassium released from a deteriorating xenogeneic liver is able to mimic a sometimes lethal cardioplegic solution. The first data coming from intra-vital microscopy herald that adhesion molecules, the newest but not last in the line of trouble-shooters, play a major role in microcirculation together with interleukins and eicosanoids (32). These adhesion molecules may, as a falsely activated system or as an incompatible system, be unable to protect the endothelial cells from the attack, adhesion and migration of white blood cells. Even when transgenic animals or other imaginative manipulations lead to the acceptance of any type of xenograft, it has to be established how far, and for how long, the products of the xenograft will be able to interact in the multifactorial orchestra. Despite this rather careful if not pessimistic appraisal, xenotransplantation has to be investigated vigorously even though the short-term outlook does not seem to be promising.