Advanced

Consistent success in life-supporting porcine cardiac xenotransplantation

Längin, Matthias; Mayr, Tanja; Reichart, Bruno; Michel, Sebastian; Buchholz, Stefan; Guethoff, Sonja; Dashkevich, Alexey; Baehr, Andrea; Egerer, Stefanie and Bauer, Andreas, et al. (2018) In Nature 564(7736). p.430-433
Abstract

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.... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature
volume
564
issue
7736
pages
4 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85058895351
ISSN
0028-0836
DOI
10.1038/s41586-018-0765-z
language
English
LU publication?
yes
id
77a28c48-6a42-4be4-9410-f94fd70c2e46
date added to LUP
2019-01-03 10:25:05
date last changed
2019-02-20 11:41:18
@article{77a28c48-6a42-4be4-9410-f94fd70c2e46,
  abstract     = {<p>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 need<sup>1–3</sup>. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative<sup>4</sup>. 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 baboons<sup>5</sup>. 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 once<sup>6</sup>. 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 xenotransplantation<sup>7</sup>.</p>},
  author       = {Längin, Matthias and Mayr, Tanja and Reichart, Bruno and Michel, Sebastian and Buchholz, Stefan and Guethoff, Sonja and Dashkevich, Alexey and Baehr, Andrea and Egerer, Stefanie and Bauer, Andreas and Mihalj, Maks and Panelli, Alessandro and Issl, Lara and Ying, Jiawei and Fresch, Ann Kathrin and Buttgereit, Ines and Mokelke, Maren and Radan, Julia and Werner, Fabian and Lutzmann, Isabelle and Steen, Stig and Sjöberg, Trygve and Paskevicius, Audrius and Qiuming, Liao and Sfriso, Riccardo and Rieben, Robert and Dahlhoff, Maik and Kessler, Barbara and Kemter, Elisabeth and Klett, Katharina and Hinkel, Rabea and Kupatt, Christian and Falkenau, Almuth and Reu, Simone and Ellgass, Reinhard and Herzog, Rudolf and Binder, Uli and Wich, Günter and Skerra, Arne and Ayares, David and Kind, Alexander and Schönmann, Uwe and Kaup, Franz Josef and Hagl, Christian and Wolf, Eckhard and Klymiuk, Nikolai and Brenner, Paolo and Abicht, Jan Michael},
  issn         = {0028-0836},
  language     = {eng},
  number       = {7736},
  pages        = {430--433},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {Consistent success in life-supporting porcine cardiac xenotransplantation},
  url          = {http://dx.doi.org/10.1038/s41586-018-0765-z},
  volume       = {564},
  year         = {2018},
}