Consistent success in life-supporting porcine cardiac xenotransplantation

Nature. 2018 Dec;564(7736):430-433. doi: 10.1038/s41586-018-0765-z. Epub 2018 Dec 5.


Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / analysis
  • Antibodies / blood
  • Complement System Proteins / analysis
  • Enzymes / blood
  • Fibrin / analysis
  • Galactosyltransferases / deficiency
  • Galactosyltransferases / genetics
  • Heart Transplantation*
  • Heterografts / pathology
  • Heterografts / transplantation*
  • Humans
  • Liver / enzymology
  • Male
  • Membrane Cofactor Protein / genetics
  • Membrane Cofactor Protein / metabolism
  • Myocardium / enzymology
  • Necrosis
  • Papio*
  • Perfusion
  • Platelet Count
  • Prothrombin Time
  • Swine*
  • Thrombomodulin / genetics
  • Thrombomodulin / metabolism
  • Time Factors
  • Transplantation, Heterologous*


  • Antibodies
  • Enzymes
  • Membrane Cofactor Protein
  • Thrombomodulin
  • Fibrin
  • Complement System Proteins
  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine