TY  - JOUR
AU  - Jebran, Ahmad-Fawad
AU  - Seidler, Tim
AU  - Tiburcy, Malte
AU  - Daskalaki, Maria
AU  - Kutschka, Ingo
AU  - Fujita, Buntaro
AU  - Ensminger, Stephan
AU  - Bremmer, Felix
AU  - Moussavi, Amir
AU  - Yang, Huaxiao
AU  - Qin, Xulei
AU  - Mißbach, Sophie
AU  - Drummer, Charis
AU  - Baraki, Hassina
AU  - Boretius, Susann
AU  - Hasenauer, Christopher
AU  - Nette, Tobias
AU  - Kowallick, Johannes
AU  - Ritter, Christian O
AU  - Lotz, Joachim
AU  - Didié, Michael
AU  - Mietsch, Mathias
AU  - Meyer, Tim
AU  - Kensah, George
AU  - Krüger, Dennis
AU  - Sakib, Sadman
AU  - Kaurani, Lalit
AU  - Fischer, Andre
AU  - Dressel, Ralf
AU  - Rodriguez-Polo, Ignacio
AU  - Stauske, Michael
AU  - Diecke, Sebastian
AU  - Maetz-Rensing, Kerstin
AU  - Gruber-Dujardin, Eva
AU  - Bleyer, Martina
AU  - Petersen, Beatrix
AU  - Roos, Christian
AU  - Zhang, Liye
AU  - Walter, Lutz
AU  - Kaulfuß, Silke
AU  - Yigit, Gökhan
AU  - Wollnik, Bernd
AU  - Levent, Elif
AU  - Roshani, Berit
AU  - Stahl-Henning, Christiane
AU  - Ströbel, Philipp
AU  - Legler, Tobias
AU  - Riggert, Joachim
AU  - Hellenkamp, Kristian
AU  - Voigt, Jens-Uwe
AU  - Hasenfuß, Gerd
AU  - Hinkel, Rabea
AU  - Wu, Joseph C
AU  - Behr, Rüdiger
AU  - Zimmermann, Wolfram-Hubertus
TI  - Engineered heart muscle allografts for heart repair in primates and humans.
JO  - Nature
VL  - 639
IS  - 8054
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DZNE-2025-00424
SP  - 503 - 511
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Macaca mulatta
KW  - Humans
KW  - Tissue Engineering: methods
KW  - Myocytes, Cardiac: transplantation
KW  - Myocytes, Cardiac: cytology
KW  - Rats
KW  - Male
KW  - Induced Pluripotent Stem Cells: cytology
KW  - Induced Pluripotent Stem Cells: transplantation
KW  - Heart Failure
KW  - Myocardium: cytology
KW  - Myocardium: pathology
KW  - Myocardial Infarction: therapy
KW  - Myocardial Infarction: surgery
KW  - Allografts
KW  - Female
KW  - Disease Models, Animal
KW  - Pericardium: transplantation
KW  - Pericardium: cytology
KW  - Rats, Nude
KW  - Myocardial Contraction
KW  - Heart: physiology
LB  - PUB:(DE-HGF)16
C6  - pmid:39880949
DO  - DOI:10.1038/s41586-024-08463-0
UR  - https://pub.dzne.de/record/277528
ER  -