Raad, Farah S.

[["dc.bibliographiccitation.artnumber","cmdc.202100222"],["dc.bibliographiccitation.firstpage","3300"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","ChemMedChem"],["dc.bibliographiccitation.lastpage","3305"],["dc.bibliographiccitation.volume","16"],["dc.contributor.affiliation","Raad, Farah S.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Khan, Taukeer A.; 2\r\nDZHK (German Center for Cardiovascular Research) – Partner site Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Esser, Tilman U.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Hudson, James E.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Seth, Bhakti Irene; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Fujita, Buntaro; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Gandamala, Ravi; 3\r\nInstitute of Organic and Biomolecular Chemistry\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Tietze, Lutz F.; 2\r\nDZHK (German Center for Cardiovascular Research) – Partner site Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zimmermann, Wolfram-Hubertus; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.author","Raad, Farah S."],["dc.contributor.author","Khan, Taukeer A."],["dc.contributor.author","Esser, Tilman U."],["dc.contributor.author","Hudson, James E."],["dc.contributor.author","Seth, Bhakti Irene"],["dc.contributor.author","Fujita, Buntaro"],["dc.contributor.author","Gandamala, Ravi"],["dc.contributor.author","Tietze, Lutz F."],["dc.contributor.author","Zimmermann, Wolfram H."],["dc.date.accessioned","2021-10-01T09:58:46Z"],["dc.date.available","2021-10-01T09:58:46Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T00:45:29Z"],["dc.description.abstract","Abstract Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small‐molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two‐tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4’‐hydroxychalcone [4’HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self‐organize into contractile engineered human myocardium (EHM). We identified 4’HC, 4‐fluoro‐4’‐methoxychalcone, and 4‐fluoro‐4’‐hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4’HC as an effective replacement for BMP4 in the derivation of contractile EHM‐forming cardiomyocytes."],["dc.description.abstract","Have a little heart: A screen for mesoderm inducing chalcones in human pluripotent stem cell cultures identified 4’‐hydroxychalcone (4’HC) as an effective replacement for bone‐morphogenetic protein 4 (BMP4) in supporting the derivation of engineered heart muscle (EHM)‐formation competent cardiomyocytes. image"],["dc.description.sponsorship","German Center for Cardiovascular Research"],["dc.description.sponsorship","German Federal Ministry for Science and Education"],["dc.description.sponsorship","German Research Foundation http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Fondation Leducq http://dx.doi.org/10.13039/501100001674"],["dc.identifier.doi","10.1002/cmdc.202100222"],["dc.identifier.pmid","34309224"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90137"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/432"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1860-7187"],["dc.relation.issn","1860-7179"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Chalcone‐Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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"]]