Xenotransplantation: back to the future?

Transpl Int. 2018 May;31(5):465-477. doi: 10.1111/tri.13104. Epub 2018 Jan 4.

Abstract

The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig-to-nonhuman-primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple-xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.

Keywords: CRISPR Cas/9; TALEN; blastocyst complementation; cell transplantation; genome editing technologies; interspecific organ generation; nonhuman primates; nucleases; safety; transplantation; xenotransplantation; xenozoonosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Gene Editing
  • Graft Rejection / etiology
  • Humans
  • Primates
  • Swine
  • Transplantation Chimera
  • Transplantation, Heterologous* / adverse effects