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000277528 037__ $$aDZNE-2025-00424
000277528 041__ $$aEnglish
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000277528 1001_ $$aJebran, Ahmad-Fawad$$b0
000277528 245__ $$aEngineered heart muscle allografts for heart repair in primates and humans.
000277528 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2025
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000277528 520__ $$aCardiomyocytes can be implanted to remuscularize the failing heart1-7. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques. After confirmation of in vitro and in vivo (nude rat model) equivalence of the newly developed rhesus macaque EHM model with a previously established Good Manufacturing Practice-compatible human EHM formulation8, long-term retention (up to 6 months) and dose-dependent enhancement of the target heart wall by EHM grafts constructed from 40 to 200 million cardiomyocytes/stromal cells were demonstrated in macaques with and without myocardial infarction-induced heart failure. In the heart failure model, evidence for EHM allograft-enhanced target heart wall contractility and ejection fraction, which are measures for local and global heart support, was obtained. Histopathological and gadolinium-based perfusion magnetic resonance imaging analyses confirmed cell retention and functional vascularization. Arrhythmia and tumour growth were not observed. The obtained feasibility, safety and efficacy data provided the pivotal underpinnings for the approval of a first-in-human clinical trial on tissue-engineered heart repair. Our clinical data confirmed remuscularization by EHM implantation in a patient with advanced heart failure.
000277528 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000277528 650_2 $$2MeSH$$aAnimals
000277528 650_2 $$2MeSH$$aMacaca mulatta
000277528 650_2 $$2MeSH$$aHumans
000277528 650_2 $$2MeSH$$aTissue Engineering: methods
000277528 650_2 $$2MeSH$$aMyocytes, Cardiac: transplantation
000277528 650_2 $$2MeSH$$aMyocytes, Cardiac: cytology
000277528 650_2 $$2MeSH$$aRats
000277528 650_2 $$2MeSH$$aMale
000277528 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: cytology
000277528 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: transplantation
000277528 650_2 $$2MeSH$$aHeart Failure
000277528 650_2 $$2MeSH$$aMyocardium: cytology
000277528 650_2 $$2MeSH$$aMyocardium: pathology
000277528 650_2 $$2MeSH$$aMyocardial Infarction: therapy
000277528 650_2 $$2MeSH$$aMyocardial Infarction: surgery
000277528 650_2 $$2MeSH$$aAllografts
000277528 650_2 $$2MeSH$$aFemale
000277528 650_2 $$2MeSH$$aDisease Models, Animal
000277528 650_2 $$2MeSH$$aPericardium: transplantation
000277528 650_2 $$2MeSH$$aPericardium: cytology
000277528 650_2 $$2MeSH$$aRats, Nude
000277528 650_2 $$2MeSH$$aMyocardial Contraction
000277528 650_2 $$2MeSH$$aHeart: physiology
000277528 7001_ $$00000-0002-6158-5087$$aSeidler, Tim$$b1
000277528 7001_ $$00000-0002-6942-6275$$aTiburcy, Malte$$b2
000277528 7001_ $$aDaskalaki, Maria$$b3
000277528 7001_ $$aKutschka, Ingo$$b4
000277528 7001_ $$aFujita, Buntaro$$b5
000277528 7001_ $$aEnsminger, Stephan$$b6
000277528 7001_ $$aBremmer, Felix$$b7
000277528 7001_ $$aMoussavi, Amir$$b8
000277528 7001_ $$aYang, Huaxiao$$b9
000277528 7001_ $$aQin, Xulei$$b10
000277528 7001_ $$aMißbach, Sophie$$b11
000277528 7001_ $$aDrummer, Charis$$b12
000277528 7001_ $$aBaraki, Hassina$$b13
000277528 7001_ $$00000-0003-2792-7423$$aBoretius, Susann$$b14
000277528 7001_ $$aHasenauer, Christopher$$b15
000277528 7001_ $$aNette, Tobias$$b16
000277528 7001_ $$aKowallick, Johannes$$b17
000277528 7001_ $$aRitter, Christian O$$b18
000277528 7001_ $$aLotz, Joachim$$b19
000277528 7001_ $$aDidié, Michael$$b20
000277528 7001_ $$aMietsch, Mathias$$b21
000277528 7001_ $$00000-0002-0521-6711$$aMeyer, Tim$$b22
000277528 7001_ $$aKensah, George$$b23
000277528 7001_ $$0P:(DE-2719)2812548$$aKrüger, Dennis$$b24
000277528 7001_ $$0P:(DE-2719)2812054$$aSakib, Sadman$$b25$$udzne
000277528 7001_ $$0P:(DE-2719)2812832$$aKaurani, Lalit$$b26$$udzne
000277528 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b27$$udzne
000277528 7001_ $$aDressel, Ralf$$b28
000277528 7001_ $$00000-0003-1254-4972$$aRodriguez-Polo, Ignacio$$b29
000277528 7001_ $$aStauske, Michael$$b30
000277528 7001_ $$00000-0002-5219-5992$$aDiecke, Sebastian$$b31
000277528 7001_ $$aMaetz-Rensing, Kerstin$$b32
000277528 7001_ $$aGruber-Dujardin, Eva$$b33
000277528 7001_ $$aBleyer, Martina$$b34
000277528 7001_ $$aPetersen, Beatrix$$b35
000277528 7001_ $$00000-0003-0190-4266$$aRoos, Christian$$b36
000277528 7001_ $$00000-0002-8829-0588$$aZhang, Liye$$b37
000277528 7001_ $$aWalter, Lutz$$b38
000277528 7001_ $$aKaulfuß, Silke$$b39
000277528 7001_ $$00000-0003-2777-0198$$aYigit, Gökhan$$b40
000277528 7001_ $$00000-0003-2589-0364$$aWollnik, Bernd$$b41
000277528 7001_ $$aLevent, Elif$$b42
000277528 7001_ $$aRoshani, Berit$$b43
000277528 7001_ $$aStahl-Henning, Christiane$$b44
000277528 7001_ $$aStröbel, Philipp$$b45
000277528 7001_ $$00000-0002-1408-5397$$aLegler, Tobias$$b46
000277528 7001_ $$aRiggert, Joachim$$b47
000277528 7001_ $$aHellenkamp, Kristian$$b48
000277528 7001_ $$00000-0002-0575-1888$$aVoigt, Jens-Uwe$$b49
000277528 7001_ $$aHasenfuß, Gerd$$b50
000277528 7001_ $$aHinkel, Rabea$$b51
000277528 7001_ $$00000-0002-6068-8041$$aWu, Joseph C$$b52
000277528 7001_ $$00000-0001-8816-6619$$aBehr, Rüdiger$$b53
000277528 7001_ $$0P:(DE-2719)9001434$$aZimmermann, Wolfram-Hubertus$$b54$$eLast author
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