Consistent success in life-supporting porcine cardiac xenotransplantation

被引：418

作者：

Laengin, Matthias ^{[1
,2
]}

Mayr, Tanja ^{[2
]}

Reichart, Bruno ^{[2
]}

Michel, Sebastian ^{[3
]}

Buchholz, Stefan ^{[3
]}

Guethoff, Sonja ^{[2
,3
]}

Dashkevich, Alexey ^{[3
]}

Baehr, Andrea ^{[1
]}

Egerer, Stefanie

Bauer, Andreas ^{[4
]}

Mihalj, Maks ^{[3
,4
]}

Panelli, Alessandro ^{[2
]}

Issl, Lara ^{[2
]}

Ying, Jiawei ^{[2
]}

Fresch, Ann Kathrin ^{[2
]}

Buttgereit, Ines ^{[2
]}

Mokelke, Maren ^{[2
]}

Radan, Julia ^{[2
]}

Werner, Fabian ^{[1
]}

Lutzmann, Isabelle ^{[2
]}

Steen, Stig ^{[5
,6
]}

Sjoberg, Trygve ^{[5
,6
]}

Paskevicius, Audrius ^{[5
,6
]}

Liao Qiuming ^{[5
,6
]}

Sfriso, Riccardo ^{[7
]}

Rieben, Robert ^{[7
]}

Dahlhoff, Maik ^{[4
]}

Kessler, Barbara ^{[4
]}

Kemter, Elisabeth ^{[4
]}

Klett, Katharina ^{[8
,9
,10
]}

Hinkel, Rabea ^{[8
,9
,10
]}

Kupatt, Christian ^{[8
,10
]}

Falkenau, Almuth ^{[11
]}

Reu, Simone ^{[12
]}

Ellgass, Reinhard ^{[3
]}

Herzog, Rudolf ^{[3
]}

Binder, Uli ^{[13
]}

Wich, Guenter ^{[14
]}

Skerra, Arne ^{[15
,16
]}

Ayares, David ^{[17
]}

Kind, Alexander ^{[18
]}

Schoenmann, Uwe ^{[19
]}

Kaup, Franz-Josef ^{[19
]}

Hagl, Christian ^{[3
]}

Wolf, Eckhard ^{[4
]}

Klymiuk, Nikolai ^{[4
]}

Brenner, Paolo ^{[2
,3
]}

Abicht, Jan-Michael ^{[1
,2
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Anaesthesiol, Munich, Germany

[2] Ludwig Maximilians Univ Munchen, Transreg Collaborat Res Ctr 127, Walter Brendel Ctr Expt Med, Munich, Germany

[3] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Cardiac Surg, Munich, Germany

[4] Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Gene Ctr, Munich, Germany

[5] Lund Univ, Dept Cardiothorac Surg, Lund, Sweden

[6] Skane Univ Hosp, Lund, Sweden

[7] Univ Bern, Dept BioMed Res DMBR, Bern, Switzerland

[8] Tech Univ Munich, I Med Klin, Klinikum Rechts Isar, Munich, Germany

[9] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, Munich, Germany

[10] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany

[11] Ludwig Maximilians Univ Munchen, Inst Vet Pathol, Munich, Germany

[12] Ludwig Maximilians Univ Munchen, Med Fac, Inst Pathol, Munich, Germany

[13] XL Prot GmbH, Freising Weihenstephan, Germany

[14] Wacker Chem AG, Munich, Germany

[15] Tech Univ Munich, Sch Life Sci Weihenstephan, Munich Ctr Integrated Prot Sci CIPS M, Munich, Germany

[16] Tech Univ Munich, Sch Life Sci Weihenstephan, Lehrstuhl Biolog Chem, Munich, Germany

[17] Revivicor, Blacksburg, VA USA

[18] Tech Univ Munich, Sch Life Sci Weihenstephan, Chair Livestock Biotechnol, Munich, Germany

[19] German Primate Ctr, Gottingen, Germany

来源：

NATURE | 2018年 / 564卷 / 7736期

关键词：

HEART-TRANSPLANTATION REPORT-2017; INTERNATIONAL SOCIETY; LUNG TRANSPLANTATION; HYPERTROPHY; EXPRESSION; COMMITTEE; ANTIBODY; REGISTRY; GROWTH;

D O I：

10.1038/s41586-018-0765-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 alternative(4). Genetically multi-modified pig hearts that lack galactose-alpha 1,3- galactose epitopes (alpha 1,3-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(5). 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(6). Here we show that alpha 1,3-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(7).

引用

页码：430 / +

页数：17

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