Consistent success in life-supporting porcine cardiac xenotransplantation

Matthias Längin; Tanja Mayr; Bruno Reichart; Sebastian Michel; Stefan Buchholz; Sonja Guethoff; Alexey Dashkevich; Andrea Baehr; Stefanie Egerer; Andreas Bauer; Maks Mihalj; Alessandro Panelli; Lara Issl; Jiawei Ying; Ann Kathrin Fresch; Ines Buttgereit; Maren Mokelke; Julia Radan; Fabian Werner; Isabelle Lutzmann; Stig Steen; Trygve Sjöberg; Audrius Paskevicius; Liao Qiuming; Riccardo Sfriso; Robert Rieben; Maik Dahlhoff; Barbara Kessler; Elisabeth Kemter; Katharina Klett; Rabea Hinkel; Christian Kupatt; Almuth Falkenau; Simone Reu; Reinhard Ellgass; Rudolf Herzog; Uli Binder; Günter Wich; Arne Skerra; David Ayares; Alexander Kind; Uwe Schönmann; Franz Josef Kaup; Christian Hagl; Eckhard Wolf; Nikolai Klymiuk; Paolo Brenner; Jan Michael Abicht

doi:10.1038/s41586-018-0765-z

Consistent success in life-supporting porcine cardiac xenotransplantation

Matthias Längin, Tanja Mayr, Bruno Reichart, Sebastian Michel, Stefan Buchholz, Sonja Guethoff, Alexey Dashkevich, Andrea Baehr, Stefanie Egerer, Andreas Bauer, Maks Mihalj, Alessandro Panelli, Lara Issl, Jiawei Ying, Ann Kathrin Fresch, Ines Buttgereit, Maren Mokelke, Julia Radan, Fabian Werner, Isabelle LutzmannStig Steen, Trygve Sjöberg, Audrius Paskevicius, Liao Qiuming, Riccardo Sfriso, Robert Rieben, Maik Dahlhoff, Barbara Kessler, Elisabeth Kemter, Katharina Klett, Rabea Hinkel, Christian Kupatt, Almuth Falkenau, Simone Reu, Reinhard Ellgass, Rudolf Herzog, Uli Binder, Günter Wich, Arne Skerra, David Ayares, Alexander Kind, Uwe Schönmann, Franz Josef Kaup, Christian Hagl, Eckhard Wolf, Nikolai Klymiuk, Paolo Brenner, Jan Michael Abicht

Research output: Contribution to journal › Article › peer-review

376 Scopus citations

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 need^1–3. 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.

Original language	English
Pages (from-to)	430-433
Number of pages	4
Journal	Nature
Volume	564
Issue number	7736
DOIs	https://doi.org/10.1038/s41586-018-0765-z
State	Published - 20 Dec 2018

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Längin, M., Mayr, T., Reichart, B., Michel, S., Buchholz, S., Guethoff, S., Dashkevich, A., Baehr, A., Egerer, S., Bauer, A., Mihalj, M., Panelli, A., Issl, L., Ying, J., Fresch, A. K., Buttgereit, I., Mokelke, M., Radan, J., Werner, F., ... Abicht, J. M. (2018). Consistent success in life-supporting porcine cardiac xenotransplantation. Nature, 564(7736), 430-433. https://doi.org/10.1038/s41586-018-0765-z

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title = "Consistent success in life-supporting porcine cardiac xenotransplantation",

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. 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.",

author = "Matthias L{\"a}ngin and Tanja Mayr and Bruno Reichart and Sebastian Michel and Stefan Buchholz and Sonja Guethoff and Alexey Dashkevich and Andrea Baehr and Stefanie Egerer and Andreas Bauer and Maks Mihalj and Alessandro Panelli and Lara Issl and Jiawei Ying and Fresch, {Ann Kathrin} and Ines Buttgereit and Maren Mokelke and Julia Radan and Fabian Werner and Isabelle Lutzmann and Stig Steen and Trygve Sj{\"o}berg and Audrius Paskevicius and Liao Qiuming and Riccardo Sfriso and Robert Rieben and Maik Dahlhoff and Barbara Kessler and Elisabeth Kemter and Katharina Klett and Rabea Hinkel and Christian Kupatt and Almuth Falkenau and Simone Reu and Reinhard Ellgass and Rudolf Herzog and Uli Binder and G{\"u}nter Wich and Arne Skerra and David Ayares and Alexander Kind and Uwe Sch{\"o}nmann and Kaup, {Franz Josef} and Christian Hagl and Eckhard Wolf and Nikolai Klymiuk and Paolo Brenner and Abicht, {Jan Michael}",

note = "Publisher Copyright: {\textcopyright} 2018, Springer Nature Limited.",

year = "2018",

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doi = "10.1038/s41586-018-0765-z",

language = "English",

volume = "564",

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Längin, M, Mayr, T, Reichart, B, Michel, S, Buchholz, S, Guethoff, S, Dashkevich, A, Baehr, A, Egerer, S, Bauer, A, Mihalj, M, Panelli, A, Issl, L, Ying, J, Fresch, AK, Buttgereit, I, Mokelke, M, Radan, J, Werner, F, Lutzmann, I, Steen, S, Sjöberg, T, Paskevicius, A, Qiuming, L, Sfriso, R, Rieben, R, Dahlhoff, M, Kessler, B, Kemter, E, Klett, K, Hinkel, R, Kupatt, C, Falkenau, A, Reu, S, Ellgass, R, Herzog, R, Binder, U, Wich, G, Skerra, A, Ayares, D, Kind, A, Schönmann, U, Kaup, FJ, Hagl, C, Wolf, E, Klymiuk, N, Brenner, P & Abicht, JM 2018, 'Consistent success in life-supporting porcine cardiac xenotransplantation', Nature, vol. 564, no. 7736, pp. 430-433. https://doi.org/10.1038/s41586-018-0765-z

TY - JOUR

T1 - Consistent success in life-supporting porcine cardiac xenotransplantation

AU - Längin, Matthias

AU - Mayr, Tanja

AU - Reichart, Bruno

AU - Michel, Sebastian

AU - Buchholz, Stefan

AU - Guethoff, Sonja

AU - Dashkevich, Alexey

AU - Baehr, Andrea

AU - Egerer, Stefanie

AU - Bauer, Andreas

AU - Mihalj, Maks

AU - Panelli, Alessandro

AU - Issl, Lara

AU - Ying, Jiawei

AU - Fresch, Ann Kathrin

AU - Buttgereit, Ines

AU - Mokelke, Maren

AU - Radan, Julia

AU - Werner, Fabian

AU - Lutzmann, Isabelle

AU - Steen, Stig

AU - Sjöberg, Trygve

AU - Paskevicius, Audrius

AU - Qiuming, Liao

AU - Sfriso, Riccardo

AU - Rieben, Robert

AU - Dahlhoff, Maik

AU - Kessler, Barbara

AU - Kemter, Elisabeth

AU - Klett, Katharina

AU - Hinkel, Rabea

AU - Kupatt, Christian

AU - Falkenau, Almuth

AU - Reu, Simone

AU - Ellgass, Reinhard

AU - Herzog, Rudolf

AU - Binder, Uli

AU - Wich, Günter

AU - Skerra, Arne

AU - Ayares, David

AU - Kind, Alexander

AU - Schönmann, Uwe

AU - Kaup, Franz Josef

AU - Hagl, Christian

AU - Wolf, Eckhard

AU - Klymiuk, Nikolai

AU - Brenner, Paolo

AU - Abicht, Jan Michael

PY - 2018/12/20

Y1 - 2018/12/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058895351&partnerID=8YFLogxK

U2 - 10.1038/s41586-018-0765-z

DO - 10.1038/s41586-018-0765-z

M3 - Article

C2 - 30518863

AN - SCOPUS:85058895351

SN - 0028-0836

VL - 564

SP - 430

EP - 433

JO - Nature

JF - Nature

IS - 7736

ER -

Consistent success in life-supporting porcine cardiac xenotransplantation

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