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Meyer, Tim
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Meyer, Tim
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Meyer, Tim
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Meyer, T.
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2019Journal Article Research Paper [["dc.bibliographiccitation.firstpage","51"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","60"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Schlick, Susanne F."],["dc.contributor.author","Spreckelsen, Florian"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Rehfeldt, Florian"],["dc.date.accessioned","2020-12-10T15:20:42Z"],["dc.date.available","2020-12-10T15:20:42Z"],["dc.date.issued","2019"],["dc.description.abstract","Cardiomyocyte and stroma cell cross-talk is essential for the formation of collagen-based engineered heart muscle, including engineered human myocardium (EHM). Fibroblasts are a main component of the myocardial stroma. We hypothesize that fibroblasts, by compacting the surrounding collagen network, support the self-organization of cardiomyocytes into a functional syncytium. With a focus on early self-organization processes in EHM, we studied the molecular and biophysical adaptations mediated by defined populations of fibroblasts and embryonic stem cell-derived cardiomyocytes in a collagen type I hydrogel. After a short phase of cell-independent collagen gelation (30 min), tissue compaction was progressively mediated by fibroblasts. Fibroblast-mediated tissue stiffening was attenuated in the presence of cardiomyocytes allowing for the assembly of stably contracting, force-generating EHM within 4 weeks. Comparative RNA-sequencing data corroborated that fibroblasts are particularly sensitive to the tissue compaction process, resulting in the fast activation of transcription profiles, supporting heart muscle development and extracellular matrix synthesis. Large amplitude oscillatory shear (LAOS) measurements revealed nonlinear strain stiffening at physiological strain amplitudes (>2%), which was reduced in the presence of cells. The nonlinear stress-strain response could be characterized by a mathematical model. Collectively, our study defines the interplay between fibroblasts and cardiomyocytes during human heart muscle self-organization in vitro and underscores the relevance of fibroblasts in the biological engineering of a cardiomyogenesis-supporting viscoelastic stroma. We anticipate that the established mathematical model will facilitate future attempts to optimize EHM for in vitro (disease modelling) and in vivo applications (heart repair)."],["dc.identifier.doi","10.1016/j.pbiomolbio.2018.11.011"],["dc.identifier.pmid","30553553"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72769"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/248"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.title","Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2019Journal Article [["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","2"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Tarantola, Marco"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Schmidt, Christoph F."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2020-12-10T15:20:42Z"],["dc.date.available","2020-12-10T15:20:42Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.pbiomolbio.2019.03.009"],["dc.identifier.issn","0079-6107"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72770"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Physics meets medicine - At the heart of active matter"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2018Journal Article Research Paper [["dc.bibliographiccitation.firstpage","127"],["dc.bibliographiccitation.journal","Journal of Pharmacological and Toxicological Methods"],["dc.bibliographiccitation.lastpage","128"],["dc.bibliographiccitation.volume","93"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Küpper, Nils"],["dc.contributor.author","Blendowske, Ralf"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2022-06-08T07:58:23Z"],["dc.date.available","2022-06-08T07:58:23Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.vascn.2018.01.429"],["dc.identifier.pii","S1056871918304337"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/110392"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-575"],["dc.relation.issn","1056-8719"],["dc.title","Inotropy and chronotropy screens in engineered human myocardium by video-optical analysis in a 48 well format"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article Research Paper [["dc.bibliographiccitation.artnumber","100032"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","STAR Protocols"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2022-02-21T15:29:53Z"],["dc.date.available","2022-02-21T15:29:53Z"],["dc.date.issued","2020"],["dc.description.abstract","This protocol describes a robust method for the generation of engineered human myocardium (EHM) from pluripotent stem cells (PSCs) in a multi-well plate under defined, serum-free conditions. By parallel culture of up to 48 EHM in one plate, contractile heart muscle can be obtained to serve numerous applications, including drug screening and disease modelling. This protocol has been successfully applied to human embryonic stem (HES) cell- and induced PSC-derived cardiomyocytes, subtype-specific, i.e., atrial and ventricular, and commercially available cardiomyocyte preparations. For complete details on the use and execution of this protocol, please refer to Tiburcy et al. (2017)."],["dc.identifier.doi","10.1016/j.xpro.2020.100032"],["dc.identifier.pmid","33111083"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100155"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/177"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/357"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2666-1667"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.rights","CC BY 4.0"],["dc.title","Generation of Engineered Human Myocardium in a Multi-well Format"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2021Journal Article Research Paper [["dc.bibliographiccitation.issue","174"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Santos, Gabriela L."],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","DeGrave, Alisa"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lutz, Susanne"],["dc.date.accessioned","2021-12-01T09:22:54Z"],["dc.date.available","2021-12-01T09:22:54Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.3791/62700"],["dc.identifier.pmid","34487119"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94508"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/338"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/402"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1940-087X"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.relation.workinggroup","RG Lutz (G Protein-Coupled Receptor Mediated Signaling)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.title","Fibroblast Derived Human Engineered Connective Tissue for Screening Applications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2019-08-21Book Chapter [["dc.bibliographiccitation.firstpage","363"],["dc.bibliographiccitation.lastpage","367"],["dc.contributor.author","Suhr, Markus"],["dc.contributor.author","Umbach, Nadine"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Sax, Ulrich"],["dc.contributor.editor","Ohno-Machado, Lucila"],["dc.contributor.editor","Séroussi, Brigitte"],["dc.date.accessioned","2022-05-13T08:13:00Z"],["dc.date.available","2022-05-13T08:13:00Z"],["dc.date.issued","2019-08-21"],["dc.description.abstract","Methods for cardiac tissue engineering and application in experiments are core technologies developed at the Institute of Pharmacology and Toxicology in Göttingen. As is the case in many academic research laboratories data capture and documentation may be improved to latest methods of digital research. A comprehensive information system infrastructure is the foundation of further advances toward automation of lab processes. A data management system concept is proposed and prototypically deployed that enables traceability of assets within the lab and reproducibility of published assays and results. The prototype integrates existing electronic lab notebook, experiment result database, and a newly introduced research data management system by means of a custom developed portal and integration component. The architecture concept and developed integration tools explore connection of routine experimental work in a biomedical research lab to a universal infrastructure of data."],["dc.identifier.doi","10.3233/SHTI190244"],["dc.identifier.pmid","31437946"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107853"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/306"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung"],["dc.relation.ispartof","MEDINFO 2019: Health and Wellbeing e-Networks for All"],["dc.relation.workinggroup","RG Nußbeck"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Cardiac Tissue Engineering as Use Case to Connect Biomedical Research Laboratories to an Emerging Global Data Infrastructure"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2022Book Chapter [["dc.bibliographiccitation.firstpage","213"],["dc.bibliographiccitation.lastpage","225"],["dc.bibliographiccitation.seriesnr","2485"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Satin, Pierre-Luc"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.editor","Coulombe, Kareen L.K."],["dc.contributor.editor","Black III, Lauren D."],["dc.date.accessioned","2022-06-01T09:39:12Z"],["dc.date.available","2022-06-01T09:39:12Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1007/978-1-0716-2261-2_14"],["dc.identifier.pmid","35618908"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108411"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/492"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/433"],["dc.notes.intern","DOI-Import GROB-572"],["dc.publisher","Springer US"],["dc.publisher.place","New York, NY"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.eisbn","978-1-0716-2261-2"],["dc.relation.isbn","978-1-0716-2260-5"],["dc.relation.ispartof","Cardiac Tissue Engineering : Methods and Protocols"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Defined Engineered Human Myocardium for Disease Modeling, Drug Screening, and Heart Repair"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2016Journal Article [["dc.bibliographiccitation.firstpage","373"],["dc.bibliographiccitation.journal","Journal of Pharmacological and Toxicological Methods"],["dc.bibliographiccitation.volume","81"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2022-03-01T11:45:25Z"],["dc.date.available","2022-03-01T11:45:25Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.vascn.2016.02.125"],["dc.identifier.pii","S105687191600126X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103317"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","1056-8719"],["dc.title","Inotropy and chronotropy screens in engineered human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]Details DOI2017Journal Article Research Paper [["dc.bibliographiccitation.firstpage","1832"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","1847"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Hudson, James E."],["dc.contributor.author","Balfanz, Paul"],["dc.contributor.author","Schlick, Susanne"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Chang Liao, Mei-Ling"],["dc.contributor.author","Levent, Elif"],["dc.contributor.author","Raad, Farah"],["dc.contributor.author","Zeidler, Sebastian"],["dc.contributor.author","Wingender, Edgar"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2022-03-01T11:43:55Z"],["dc.date.available","2022-03-01T11:43:55Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: Advancing structural and functional maturation of stem cell–derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. Methods: We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell–derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results: EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions: We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell–derived cardiomyocytes under defined, serum-free conditions."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.116.024145"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102873"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/162"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]Details DOI2014Book Chapter [["dc.bibliographiccitation.firstpage","167"],["dc.bibliographiccitation.lastpage","176"],["dc.bibliographiccitation.seriesnr","1181"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Soong, Poh Loong"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:54:28Z"],["dc.date.available","2017-09-07T11:54:28Z"],["dc.date.issued","2014"],["dc.description.abstract","Cardiac muscle engineering has evolved over nearly 20 years from a scientific oddity to a mainstream technology with a wide range of applications. Of the many published methods it appears that hydrogels constitute the preferred scaffolds for myocardial tissue engineering and support of organotypic development. Here we describe a simple and highly robust protocol for the generation of engineered heart muscle using a collagen-based hydrogel method."],["dc.identifier.doi","10.1007/978-1-4939-1047-2_15"],["dc.identifier.gro","3145187"],["dc.identifier.pmid","25070336"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2895"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/63"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.publisher","Humana Press"],["dc.publisher.place","New York"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.isbn","978-1-4939-1046-5"],["dc.relation.ispartof","Cardiac Tissue Engineering"],["dc.relation.ispartofseries","Methods in Molecular Biology;1181"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Collagen-Based Engineered Heart Muscle"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]Details DOI PMID PMC