Molecular targets for genetic engineering in pig-to-human vascularized xenotransplantation

  • Bernard Vanhove
  • Jean-Paul Soulillou
Part of the Transplantation and Clinical Immunology book series (TRAC, volume 29)


Over the past few years, our understanding of the mechanisms involved in the rejection of discordant xenografts has greatly increased. Several molecules potentially involved in the rejection process have been identified, and the way in which they mediate their pathologic effect largely elucidated. At the same time, improvements in the technology of transgenesis in the pig have made it possible to produce donor animals expressing some of these molecules, particularly on endothelial cells, so that their actual role in the process of pig-to-primate xenograft rejection can be evaluated. One factor limiting genetic manipulation in pigs, however, is that the embryonic stem cells necessary for homologous recombination are currently unavailable, which makes it impossible to knock out a gene in that species. Emerging techniques such as intrabody-mediated phenotypic knockout, overexpression of dominant negative mutants, anti-sense RNA or ribozymes may represent alternatives and result in the production of donor animals with reduced expression of factors that initiate rejection. It is our assumption that combined expression of several protective transgenes associated with reduced expression of some of the endogenous proteins that promote rejection will make it possible to maintain a pig organ in the human body.


Tissue Factor Pathway Inhibitor Hyperacute Rejection Porcine Endothelial Cell Delay Xenograft Rejection Discordant Xenograft 


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© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Bernard Vanhove
  • Jean-Paul Soulillou

There are no affiliations available

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