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Pig-to-non-human primate heart transplantation : The final step toward clinical xenotransplantation?

Reichart, Bruno ; Längin, Matthias ; Radan, Julia ; Mokelke, Maren ; Buttgereit, Ines ; Ying, Jiawei ; Fresch, Ann Kathrin ; Mayr, Tanja ; Issl, Lara and Buchholz, Stefan , et al. (2020) In Journal of Heart and Lung Transplantation 39(8). p.751-757
Abstract

Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2... (More)

Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions: The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
costimulation blockade, graft growth, heart preservation, orthotopic heart transplantation, xenotransplantation
in
Journal of Heart and Lung Transplantation
volume
39
issue
8
pages
7 pages
publisher
Elsevier
external identifiers
  • pmid:32527674
  • scopus:85086102864
ISSN
1053-2498
DOI
10.1016/j.healun.2020.05.004
language
English
LU publication?
yes
id
b43ac76b-aa58-49bb-be89-0033c84c33f1
date added to LUP
2020-07-02 13:51:32
date last changed
2024-04-03 09:12:11
@article{b43ac76b-aa58-49bb-be89-0033c84c33f1,
  abstract     = {{<p>Background: The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results: The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions: The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.</p>}},
  author       = {{Reichart, Bruno and Längin, Matthias and Radan, Julia and Mokelke, Maren and Buttgereit, Ines and Ying, Jiawei and Fresch, Ann Kathrin and Mayr, Tanja and Issl, Lara and Buchholz, Stefan and Michel, Sebastian and Ellgass, Reinhard and Mihalj, Maks and Egerer, Stefanie and Baehr, Andrea and Kessler, Barbara and Kemter, Elisabeth and Kurome, Mayuko and Zakhartchenko, Valeri and Steen, Stig and Sjöberg, Trygve and Paskevicius, Audrius and Krüger, Luise and Fiebig, Uwe and Denner, Joachim and Godehardt, Antonia W. and Tönjes, Ralf R. and Milusev, Anastasia and Rieben, Robert and Sfriso, Riccardo and Walz, Christoph and Kirchner, Thomas and Ayares, David and Lampe, Karen and Schönmann, Uwe and Hagl, Christian and Wolf, Eckhard and Klymiuk, Nikolai and Abicht, Jan Michael and Brenner, Paolo}},
  issn         = {{1053-2498}},
  keywords     = {{costimulation blockade; graft growth; heart preservation; orthotopic heart transplantation; xenotransplantation}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{751--757}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Heart and Lung Transplantation}},
  title        = {{Pig-to-non-human primate heart transplantation : The final step toward clinical xenotransplantation?}},
  url          = {{http://dx.doi.org/10.1016/j.healun.2020.05.004}},
  doi          = {{10.1016/j.healun.2020.05.004}},
  volume       = {{39}},
  year         = {{2020}},
}