Biblioteca
Web espaņola de trasplantes

Xenotransplantation

Only 110 3 patients will receive the organ they need this year. Potentially, xenotransplantation could provide enough healthy organs to otter transplantation to thousands ot patients on waiting lists worldwide Although there are many technical problems to he overcome in order to reach this goal, encouraging progress was reported at this meeting. David White (Imutran/Novartis, UK) reported that, through the development ot transgenic pigs that express human regulators ot complement activity, the major immunological harrier to xenotransplantation, hyperacute rejection, has been overcome. Studies involving transplanting transgenic pig kidneys and hearts into non-human primates have contirmed this tact, and have also shown that these transgenic pig organs can support life. Research is now tocusing on immunological issues, and in particular on refining the immunosuppressive protocols that will he used to prevent subsequent acute vascular and cellular rejection.

imagen6.jpg (24280 bytes)

" Xenotransplantacion could provide enough healthy organs to offer transplantation to thousands
of patients on waiting lists wordwide "

A number ot different immunosuppressive strategies are currently heing evaluated, and in one particular study in which the non-human primate recipients were splenectomised after transplantation of transgenic pig kidneys, survival times ot up to 11 weeks have been achieved.  

There has been much discussion about the satety issues raised by xenotransplantation, particularly with regard to the potential tor cross species transmission by the porcine endogenous retrovirus (POERV). Betore proceeding with clinical xenotransplantation, it must be clearly established whether it is possible tor the PoEPV to be transferred 10 vivo to non-human primate cells, and it so, whether it is pathogenic to the organ recipient. Gillian Langtord (Imutran/Novartis, UK) described variants of the PoERV that have been isolated to date. Co-culture studies, in which pig kidney cell lines that spontaneously release the PoERVs have been co-cultivated with a variety ot human cell lines, have shown that two ot the tour variants can infect human cells. Using the sequence information derived from these variants, probes have been designed to characterise the PoERVs present within a particular herd of transgenic pigs. Two studies have been initiated by Novartis to assess the possibility that tollowing xenotransplantation PoERVs could cross the species barrier.

imagen7.jpg (37284 bytes)

The tirst ot these studies involves employing extremely sensitive PCR and RT-PCR techniques to analyse tissue samples from primates that have been transplanted with transgenic pig organs. In addition, serum trom these primates will be analysed tor evidence of antibody responses against PoFRV The second study involves analysing blood samples from patients who have been exposed to living porcine  tissues. Over 170transcriptase samples have been collected trom patients whose blood has been pertused through either pig kidneys, spleens or livers or who have received fetal neural cells or porcine islets. Discussion at the meeting suggested that, despite some technical limitations of the proposed testing strategy, these two studies will be particularly relevant in determining the risks associated with PoFRVs and transplantation. Jeft Platt (Duke University, North Carolina, USA) predicted that 'permanent' xenotransplantation would not be achieved or accepted tor some years, but that in the interim there may be several important steps. First, there will be tissue xenogratts and extracorporeal use ot organs, tollowed by use ot teniporary transplants as bridges to scarce allogratts, and then permanent transplants in patients who cannot receive a human organ allogratt. Unly after this stage will xenogratts be accepted as a true alternative to allotransplantation.It appears that a great deal of progress is being made in this exciting area which otters the potential to make transplantation available to all those in need.