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@ARTICLE{Jebran:277528,
author = {Jebran, Ahmad-Fawad and Seidler, Tim and Tiburcy, Malte and
Daskalaki, Maria and Kutschka, Ingo and Fujita, Buntaro and
Ensminger, Stephan and Bremmer, Felix and Moussavi, Amir and
Yang, Huaxiao and Qin, Xulei and Mißbach, Sophie and
Drummer, Charis and Baraki, Hassina and Boretius, Susann and
Hasenauer, Christopher and Nette, Tobias and Kowallick,
Johannes and Ritter, Christian O and Lotz, Joachim and
Didié, Michael and Mietsch, Mathias and Meyer, Tim and
Kensah, George and Krüger, Dennis and Sakib, Sadman and
Kaurani, Lalit and Fischer, Andre and Dressel, Ralf and
Rodriguez-Polo, Ignacio and Stauske, Michael and Diecke,
Sebastian and Maetz-Rensing, Kerstin and Gruber-Dujardin,
Eva and Bleyer, Martina and Petersen, Beatrix and Roos,
Christian and Zhang, Liye and Walter, Lutz and Kaulfuß,
Silke and Yigit, Gökhan and Wollnik, Bernd and Levent, Elif
and Roshani, Berit and Stahl-Henning, Christiane and
Ströbel, Philipp and Legler, Tobias and Riggert, Joachim
and Hellenkamp, Kristian and Voigt, Jens-Uwe and Hasenfuß,
Gerd and Hinkel, Rabea and Wu, Joseph C and Behr, Rüdiger
and Zimmermann, Wolfram-Hubertus},
title = {{E}ngineered heart muscle allografts for heart repair in
primates and humans.},
journal = {Nature},
volume = {639},
number = {8054},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DZNE-2025-00424},
pages = {503 - 511},
year = {2025},
abstract = {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.},
keywords = {Animals / Macaca mulatta / Humans / Tissue Engineering:
methods / Myocytes, Cardiac: transplantation / Myocytes,
Cardiac: cytology / Rats / Male / Induced Pluripotent Stem
Cells: cytology / Induced Pluripotent Stem Cells:
transplantation / Heart Failure / Myocardium: cytology /
Myocardium: pathology / Myocardial Infarction: therapy /
Myocardial Infarction: surgery / Allografts / Female /
Disease Models, Animal / Pericardium: transplantation /
Pericardium: cytology / Rats, Nude / Myocardial Contraction
/ Heart: physiology},
cin = {AG Fischer},
ddc = {500},
cid = {I:(DE-2719)1410002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39880949},
doi = {10.1038/s41586-024-08463-0},
url = {https://pub.dzne.de/record/277528},
}