Home > Publications Database > Engineered heart muscle allografts for heart repair in primates and humans. > print

001     277528
005     20250323000958.0
024 7 _ |a 10.1038/s41586-024-08463-0
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024 7 _ |a pmid:39880949
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024 7 _ |a 0028-0836
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024 7 _ |a 1476-4687
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024 7 _ |a altmetric:173616664
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037 _ _ |a DZNE-2025-00424
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Jebran, Ahmad-Fawad
|b 0
245 _ _ |a Engineered heart muscle allografts for heart repair in primates and humans.
260 _ _ |a London [u.a.]
|c 2025
|b Nature Publ. Group
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Cardiomyocytes can be implanted to remuscularize the failing heart1-7. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques. After confirmation of in vitro and in vivo (nude rat model) equivalence of the newly developed rhesus macaque EHM model with a previously established Good Manufacturing Practice-compatible human EHM formulation8, long-term retention (up to 6 months) and dose-dependent enhancement of the target heart wall by EHM grafts constructed from 40 to 200 million cardiomyocytes/stromal cells were demonstrated in macaques with and without myocardial infarction-induced heart failure. In the heart failure model, evidence for EHM allograft-enhanced target heart wall contractility and ejection fraction, which are measures for local and global heart support, was obtained. Histopathological and gadolinium-based perfusion magnetic resonance imaging analyses confirmed cell retention and functional vascularization. Arrhythmia and tumour growth were not observed. The obtained feasibility, safety and efficacy data provided the pivotal underpinnings for the approval of a first-in-human clinical trial on tissue-engineered heart repair. Our clinical data confirmed remuscularization by EHM implantation in a patient with advanced heart failure.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Macaca mulatta
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Tissue Engineering: methods
|2 MeSH
650 _ 2 |a Myocytes, Cardiac: transplantation
|2 MeSH
650 _ 2 |a Myocytes, Cardiac: cytology
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: cytology
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: transplantation
|2 MeSH
650 _ 2 |a Heart Failure
|2 MeSH
650 _ 2 |a Myocardium: cytology
|2 MeSH
650 _ 2 |a Myocardium: pathology
|2 MeSH
650 _ 2 |a Myocardial Infarction: therapy
|2 MeSH
650 _ 2 |a Myocardial Infarction: surgery
|2 MeSH
650 _ 2 |a Allografts
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Pericardium: transplantation
|2 MeSH
650 _ 2 |a Pericardium: cytology
|2 MeSH
650 _ 2 |a Rats, Nude
|2 MeSH
650 _ 2 |a Myocardial Contraction
|2 MeSH
650 _ 2 |a Heart: physiology
|2 MeSH
700 1 _ |a Seidler, Tim
|0 0000-0002-6158-5087
|b 1
700 1 _ |a Tiburcy, Malte
|0 0000-0002-6942-6275
|b 2
700 1 _ |a Daskalaki, Maria
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700 1 _ |a Kutschka, Ingo
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700 1 _ |a Fujita, Buntaro
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700 1 _ |a Ensminger, Stephan
|b 6
700 1 _ |a Bremmer, Felix
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700 1 _ |a Moussavi, Amir
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700 1 _ |a Yang, Huaxiao
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700 1 _ |a Qin, Xulei
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700 1 _ |a Mißbach, Sophie
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700 1 _ |a Drummer, Charis
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700 1 _ |a Baraki, Hassina
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700 1 _ |a Boretius, Susann
|0 0000-0003-2792-7423
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700 1 _ |a Hasenauer, Christopher
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700 1 _ |a Nette, Tobias
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700 1 _ |a Kowallick, Johannes
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700 1 _ |a Ritter, Christian O
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700 1 _ |a Lotz, Joachim
|b 19
700 1 _ |a Didié, Michael
|b 20
700 1 _ |a Mietsch, Mathias
|b 21
700 1 _ |a Meyer, Tim
|0 0000-0002-0521-6711
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700 1 _ |a Kensah, George
|b 23
700 1 _ |a Krüger, Dennis
|0 P:(DE-2719)2812548
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700 1 _ |a Sakib, Sadman
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700 1 _ |a Kaurani, Lalit
|0 P:(DE-2719)2812832
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700 1 _ |a Fischer, Andre
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700 1 _ |a Dressel, Ralf
|b 28
700 1 _ |a Rodriguez-Polo, Ignacio
|0 0000-0003-1254-4972
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700 1 _ |a Stauske, Michael
|b 30
700 1 _ |a Diecke, Sebastian
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700 1 _ |a Maetz-Rensing, Kerstin
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700 1 _ |a Gruber-Dujardin, Eva
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700 1 _ |a Bleyer, Martina
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700 1 _ |a Petersen, Beatrix
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700 1 _ |a Roos, Christian
|0 0000-0003-0190-4266
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700 1 _ |a Zhang, Liye
|0 0000-0002-8829-0588
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700 1 _ |a Walter, Lutz
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700 1 _ |a Kaulfuß, Silke
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700 1 _ |a Yigit, Gökhan
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700 1 _ |a Wollnik, Bernd
|0 0000-0003-2589-0364
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700 1 _ |a Levent, Elif
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700 1 _ |a Roshani, Berit
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700 1 _ |a Stahl-Henning, Christiane
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700 1 _ |a Ströbel, Philipp
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700 1 _ |a Legler, Tobias
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700 1 _ |a Riggert, Joachim
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700 1 _ |a Hellenkamp, Kristian
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700 1 _ |a Voigt, Jens-Uwe
|0 0000-0002-0575-1888
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700 1 _ |a Hasenfuß, Gerd
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700 1 _ |a Hinkel, Rabea
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700 1 _ |a Wu, Joseph C
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700 1 _ |a Behr, Rüdiger
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700 1 _ |a Zimmermann, Wolfram-Hubertus
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773 _ _ |a 10.1038/s41586-024-08463-0
|g Vol. 639, no. 8054, p. 503 - 511
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