Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?
- Reichart B Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany. Electronic address: bruno.reichart@med.uni-muenchen.de.
- Längin M Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
- Radan J Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Mokelke M Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Buttgereit I Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Ying J Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Fresch AK Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Mayr T Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
- Issl L Transregional Collaborative Research Center, Walter Brendel Center of Experimental Medicine, LMU Munich, Munich, Germany.
- Buchholz S Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
- Michel S Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
- Ellgass R Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
- Mihalj M Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Egerer S Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Baehr A Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Kessler B Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Kemter E Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Kurome M Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Zakhartchenko V Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Steen S Department of Cardiothoracic Surgery, Lunds University and Skåne University Hospital, Lund, Sweden.
- Sjöberg T Department of Cardiothoracic Surgery, Lunds University and Skåne University Hospital, Lund, Sweden.
- Paskevicius A Department of Cardiothoracic Surgery, Lunds University and Skåne University Hospital, Lund, Sweden.
- Krüger L Robert Koch Institute, Berlin, Germany.
- Fiebig U Robert Koch Institute, Berlin, Germany.
- Denner J Robert Koch Institute, Berlin, Germany.
- Godehardt AW Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
- Tönjes RR Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
- Milusev A Department for BioMedical Research, University of Bern, Bern, Switzerland.
- Rieben R Department for BioMedical Research, University of Bern, Bern, Switzerland.
- Sfriso R Department for BioMedical Research, University of Bern, Bern, Switzerland.
- Walz C Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.
- Kirchner T Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.
- Ayares D Revivicor, Blacksburg, Virginia.
- Lampe K German Primate Center, Göttingen, Germany.
- Schönmann U German Primate Center, Göttingen, Germany.
- Hagl C Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
- Wolf E Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Klymiuk N Gene Center, Institute of Molecular Animal Breeding and Biotechnology, LMU Munich, Munich, Germany.
- Abicht JM Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
- Brenner P Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany.
- 2020-06-13
Published in:
- The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - 2020
costimulation blockade
graft growth
heart preservation
orthotopic heart transplantation
xenotransplantation
English
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.
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.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.healun.2020.05.004
- PMID 32527674
- Persistent URL
- https://sonar.ch/global/documents/279162
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