Journal ArticleDOI
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,I. Lutzmann,Stig Steen,Trygve Sjöberg,Audrius Paskevicius,Liao Qiuming,Riccardo Sfriso,Robert Rieben,Maik Dahlhoff,Barbara Kessler,Elisabeth Kemter,Mayuko Kurome,Valeri Zakhartchenko,Katharina Klett,Katharina Klett,Rabea Hinkel,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 +51 more
Reads0
Chats0
TLDR
It is shown that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model.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.read more
Citations
More filters
Journal ArticleDOI
Xenotransplantation: Current Status in Preclinical Research.
TL;DR: Current understanding of the immunological mechanisms involved in xenograft rejection, genetically modified pigs used for xenotransplantation, and progress that has been made in developing pig-to-pig- to-non-human primate models are focused on.
Journal ArticleDOI
Transplanting organs from pigs to humans.
Megan Sykes,David H. Sachs +1 more
TL;DR: The potential and limitations of modifications of pigs genetically and how the engineering of the graft can be leveraged to alter the host immune response so that all types of immune attack are avoided are discussed.
Journal ArticleDOI
Ferroptosis and Necroptosis in the Kidney.
TL;DR: It is hypothesized that necroptosis might initiate cell death propagation through ferroptosis, and the remaining necrotic debris requires effective removal processes to prevent a secondary inflammatory response, referred to as necroinflammation.
Journal ArticleDOI
The pig as a model for immunology research
TL;DR: After genetic modifications are established, the pig is the best animal model for future xenotransplantation to reduce the problem of organ shortage for organ transplantation.
Journal ArticleDOI
Justification of specific genetic modifications in pigs for clinical organ xenotransplantation.
David K. C. Cooper,Hidetaka Hara,Hayato Iwase,Takayuki Yamamoto,Qi Li,Qi Li,Mohamed Ezzelarab,Elena A. Federzoni,Amy Dandro,David Ayares +9 more
TL;DR: It is suggested that a pig with nine genetic modifications will provide organs that would function for a clinically valuable period of time, for example, >12 months, after transplantation into patients with end‐stage organ failure.
References
More filters
Journal ArticleDOI
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
Roberto M. Lang,Michelle Bierig,Richard B. Devereux,Frank A. Flachskampf,Elyse Foster,Patricia A. Pellikka,Michael H. Picard,Mary J. Roman,James B. Seward,Jack S. Shanewise,Scott D. Solomon,Kirk T. Spencer,Martin St. John Sutton,William J. Stewart +13 more
TL;DR: Members of the Chamber Quantification Writing Group are: Roberto M. Lang, MD, Fase, Michelle Bierig, MPH, RDCS, FASE, Richard B. Devereux,MD, Frank A. Flachskampf, MD and Elyse Foster, MD.
Journal ArticleDOI
Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings
Richard B. Devereux,Richard B. Devereux,Daniel R. Alonso,Daniel R. Alonso,Elizabeth M. Lutas,Elizabeth M. Lutas,Geoffrey J. Gottlieb,Geoffrey J. Gottlieb,E Campo,E Campo,Irene Sachs,Irene Sachs,Nathaniel Reichek,Nathaniel Reichek +13 more
TL;DR: To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem e chocardiograms were compared with LV mass measurements made at necropsy in 55 patients.
Journal ArticleDOI
mTOR Signaling in Growth, Metabolism, and Disease.
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR signaling network contributes to human disease is highlighted.
Journal ArticleDOI
The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Heart Transplantation Report—2017; Focus Theme: Allograft ischemic time
Daniel C. Chambers,Roger D. Yusen,Wida S. Cherikh,Samuel B. Goldfarb,Anna Y. Kucheryavaya,Kiran Khusch,Bronwyn Levvey,Lars Lund,Bruno Meiser,Joseph W. Rossano,Josef Stehlik +10 more
Journal ArticleDOI
Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience.
Kenji Kuwaki,Yau Lin Tseng,Frank J. M. F. Dor,Akira Shimizu,Stuart L. Houser,T.M. Sanderson,Courtney J. Lancos,Derek D. Prabharasuth,Jane Cheng,K Moran,Yosuke Hisashi,Nicolas J. Mueller,Kazuhiko Yamada,Julia L. Greenstein,Robert J. Hawley,Clive Patience,Michel Awwad,Jay A. Fishman,Simon C. Robson,Henk Jan Schuurman,David H. Sachs,David K. C. Cooper,David K. C. Cooper +22 more
TL;DR: The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies and the elimination of the galactose-α1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2–6 months.