Eschenhagen, Thomas

[["dc.bibliographiccitation.firstpage","452"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","458"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Wasmeier, Gerald H."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Nixdorff, U"],["dc.contributor.author","Hess, Andreas"],["dc.contributor.author","Budinsky, L."],["dc.contributor.author","Brune, K"],["dc.contributor.author","Michaelis, B."],["dc.contributor.author","Dhein, S."],["dc.contributor.author","Schwoerer, Alexander Peter"],["dc.contributor.author","Ehmke, Heimo"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:53:08Z"],["dc.date.available","2017-09-07T11:53:08Z"],["dc.date.issued","2006"],["dc.description.abstract","The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/ diameter, 1-4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts."],["dc.identifier.doi","10.1038/nm1394"],["dc.identifier.gro","3143714"],["dc.identifier.isi","000236581300035"],["dc.identifier.pmid","16582915"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1259"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","223"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","230"],["dc.bibliographiccitation.volume","90"],["dc.contributor.author","Zimmermann, W.-H."],["dc.contributor.author","Schneiderbanger, K."],["dc.contributor.author","Schubert, P."],["dc.contributor.author","Didié, M."],["dc.contributor.author","Münzel, F."],["dc.contributor.author","Heubach, J."],["dc.contributor.author","Kostin, S."],["dc.contributor.author","Neuhuber, W. L."],["dc.contributor.author","Eschenhagen, T."],["dc.date.accessioned","2017-09-07T11:45:56Z"],["dc.date.available","2017-09-07T11:45:56Z"],["dc.date.issued","2002"],["dc.description.abstract","Cardiac tissue engineering is an emerging field. The suitability of engineered heart tissue (EHT) for both in vitro and in vivo applications will depend on the degree of syncytoid tissue formation and cardiac myocyte differentiation in vitro, contractile function, and electrophysiological properties. Here, we demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I and matrix factors, cast in circular molds, and subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs that display important hallmarks of differentiated myocardium. Comparative histological analysis of EHTs with native heart tissue from newborn, 6-day-old, and adult rats revealed that cardiac cells in EHTs reconstitute intensively interconnected, longitudinally oriented, cardiac muscle bundles with morphological features resembling adult rather than immature native tissue. Confocal and electron microscopy demonstrated characteristic features of native differentiated myocardium; some of these features are absent in myocytes from newborn rats: (1) highly organized sarcomeres in registry; (2) adherens junctions, gap junctions, and desmosomes; (3) a well-developed T-tubular system and dyad formation with the sarcoplasmic reticulum; and (4) a basement membrane surrounding cardiac myocytes. Accordingly, EHTs displayed contractile characteristics of native myocardium with a high ratio of twitch (0.4 to 0.8 mN) to resting tension (0.1 to 0.3 mN) and a strong beta-adrenergic inotropic response. Action potential recordings demonstrated stable resting membrane potentials of -66 to -78 mV, fast upstroke kinetics, and a prominent plateau phase. The data indicate that EHTs represent highly differentiated cardiac tissue constructs, making EHTs a promising material for in vitro studies of cardiac function and tissue replacement therapy."],["dc.identifier.doi","10.1161/hh0202.103644"],["dc.identifier.gro","3144219"],["dc.identifier.isi","000173821800018"],["dc.identifier.pmid","11834716"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1819"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0009-7330"],["dc.title","Tissue engineering of a differentiated cardiac muscle construct"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Christalla, P."],["dc.contributor.author","Rau, T."],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Schumacher, U."],["dc.contributor.author","Lin, Qiong"],["dc.contributor.author","Zenke, Martin"],["dc.contributor.author","Zimmmermann, W. H."],["dc.date.accessioned","2018-11-07T08:41:33Z"],["dc.date.available","2018-11-07T08:41:33Z"],["dc.date.issued","2010"],["dc.format.extent","S45"],["dc.identifier.isi","000282114100008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19493"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.conference","Conference on Frontiers in Cardiovascular Biology"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0008-6363"],["dc.title","Pluripotent parthenogenetic stem cells with a cardiogenic potential can be generated to express heterozygous and homozygous major histocompatibility complexes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1105"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","U46"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Boy, Oliver"],["dc.contributor.author","Christalla, Peter"],["dc.contributor.author","Doeker, Stephan"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Karikkineth, Bijoy Chandapillai"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Grimm, Michael"],["dc.contributor.author","Nose, Monika"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Yin, Xiaoke"],["dc.contributor.author","Mayr, Manuel"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:43:18Z"],["dc.date.available","2017-09-07T11:43:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Rationale: Cardiac tissue engineering should provide \"realistic\" in vitro heart muscle models and surrogate tissue for myocardial repair. For either application, engineered myocardium should display features of native myocardium, including terminal differentiation, organotypic maturation, and hypertrophic growth. Objective: To test the hypothesis that 3D-engineered heart tissue (EHT) culture supports (1) terminal differentiation as well as (2) organotypic assembly and maturation of immature cardiomyocytes, and (3) constitutes a methodological platform to investigate mechanisms underlying hypertrophic growth. Methods and Results: We generated EHTs from neonatal rat cardiomyocytes and compared morphological and molecular properties of EHT and native myocardium from fetal, neonatal, and adult rats. We made the following key observations: cardiomyocytes in EHT (1) gained a high level of binucleation in the absence of notable cytokinesis, (2) regained a rod-shape and anisotropic sarcomere organization, (3) demonstrated a fetal-to-adult gene expression pattern, and (4) responded to distinct hypertrophic stimuli with concentric or eccentric hypertrophy and reexpression of fetal genes. The process of terminal differentiation and maturation (culture days 7-12) was preceded by a tissue consolidation phase (culture days 0-7) with substantial cardiomyocyte apoptosis and dynamic extracellular matrix restructuring. Conclusions: This study documents the propensity of immature cardiomyocytes to terminally differentiate and mature in EHT in a remarkably organotypic manner. It moreover provides the rationale for the utility of the EHT technology as a methodological bridge between 2D cell culture and animal models. (Circ Res. 2011;109:1105-1114.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.111.251843"],["dc.identifier.gro","3142637"],["dc.identifier.isi","000296417200005"],["dc.identifier.pmid","21921264"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7826"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Terminal Differentiation, Advanced Organotypic Maturation, and Modeling of Hypertrophic Growth in Engineered Heart Tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","419"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","429"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Doeker, Stephan"],["dc.contributor.author","Melnychenko, Ivan"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Rogge, Christina"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:52:36Z"],["dc.date.available","2017-09-07T11:52:36Z"],["dc.date.issued","2006"],["dc.description.abstract","Cardiac muscle engineering aims at providing functional myocardium to repair diseased hearts and model cardiac development, physiology.. and disease in vitro. Several enabling technologies have been established over the past 10 years to create functional myocardium. Although none of the presently employed technologies yields a perfect match of natural heart muscle, it can be anticipated that human heart muscle equivalents will become available after fine tuning of currently established tissue engineering concepts. This review provides an update on the state of cardiac muscle engineering and its utilization in cardiac regeneration. We discuss the application of stem cells including the allocation of autologous cell material, transgenic technologies that may improve tissue structure as well as in vivo engraftment, and vascularization concepts. We also touch on legal and economic aspects that have to be considered before engineered myocardium may eventually be applied in patients and discuss who may be a potential recipient. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.cardiores.2006.03.023"],["dc.identifier.gro","3143648"],["dc.identifier.isi","000239883900007"],["dc.identifier.pmid","16697358"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1185"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0008-6363"],["dc.title","Heart muscle engineering: An update on cardiac muscle replacement therapy"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","I146"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.lastpage","I152"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Didié, Michael"],["dc.contributor.author","Münzel, Felix"],["dc.contributor.author","Schubert, Pia"],["dc.contributor.author","Schneiderbanger, Karin"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:54:29Z"],["dc.date.available","2017-09-07T11:54:29Z"],["dc.date.issued","2002"],["dc.description.abstract","Myocardial infarction results in irreversible loss of cardiac myocytes and heart failure. Tissue or cell grafting offers the prospect of reintroducing contractile elements into impaired hearts. However, implanted cardiac myocytes remain physically and electrically isolated from the viable myocardium. Accordingly, the proof of increased contractile function attributable specifically to cell grafting procedures is sparse. Over the last few years, we have developed a new method to generate three-dimensional engineered heart tissue (EHTs) in vitro from embryonic chick or neonatal rat cardiac myocytes. EHTs comprise functional and morphological properties of intact myocardium. We hypothesized that EHTs, preformed in vitro into suitable geometric forms, represent appropriate graft material for in vivo tissue repair with advantages over isolated cells. Herein we describe initial results from implantation experiments of EHTs in the peritoneum of Fisher 344 rats. EHTs survived for at least 14 days, maintained a network of differentiated cardiac myocytes, and were strongly vascularized. Thus, the present study provides the first evidence for the general feasibility of EHTs as material for a novel tissue replacement approach."],["dc.identifier.doi","10.1007/s003950200043"],["dc.identifier.gro","3145180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2887"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0300-8428"],["dc.title","3D engineered heart tissue for replacement therapy"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","371"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","376"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Singh, Jasmin"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Laatsch, Alexander"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.date.accessioned","2017-09-07T11:49:25Z"],["dc.date.available","2017-09-07T11:49:25Z"],["dc.date.issued","2007"],["dc.description.abstract","PKC alpha has been shown to be a negative regulator of contractility and PKCa gene deletion in mice protected against heart failure. Small interfering (si)RNAs mediate gene silencing by RNA interference (RNAi) and may be used to knockdown PKC alpha in cardiomyocytes. However, transfection efficiencies of (si)RNAs by lipofection tend to be low in primary cells. To address this limitation, we developed an adenoviral vector (AV) driving short hairpin (sh)RNAs against PKCa (Ad-shPKC alpha) and evaluated its potential to silence PKCa in neonatal rat cardiac myocytes and in engineered heart tissues (EHTs), which resemble functional myocardium in vitro. A nonsense encoding AV (Ad-shNS) served as control. Quantitative PCR and Western blotting showed 90% lower PKC alpha.-mRNA and 50% lower PKC alpha protein in Ad-shPKC alpha-infected cells. EHTs were infected with Ad-shPKCa on day I I and subjected to isometric force measurements in organ baths 4 days later. Mean twitch tension was > 50% higher in Ad-shPKC alpha compared to Ad-shNS-infected EHTs, under basal and Ca2+- or isoprenaline-stimulated conditions. Twitch tension negatively correlated with PKCa mRNA levels. In summary, AV-delivered shRNA mediated highly efficient PKCa knockdown in cardiac myocytes and improved contractility in EHTs. The data support a role of PKC alpha as a negative regulator of myocardial contractility and demonstrate that EHTs in conjunction with AV-delivered shRNA are a useful model for target validation. (c) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2007.05.021"],["dc.identifier.gro","3143445"],["dc.identifier.isi","000249611300016"],["dc.identifier.pmid","17628588"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/960"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","Adenovirus-delivered short hairpin RNA targeting contractile function in reconstituted heart PKC alpha improves tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","I16"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.lastpage","I23"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Yildirim, Yalin"],["dc.contributor.author","Naito, Hiroshi"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Karikkineth, Bijoy Chandapillai"],["dc.contributor.author","Biermann, Daniel"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:49:25Z"],["dc.date.available","2017-09-07T11:49:25Z"],["dc.date.issued","2007"],["dc.description.abstract","Background - Engineered heart tissue (EHT) can be generated from cardiomyocytes and extracellular matrix proteins and used to repair local heart muscle defects in vivo. Here, we hypothesized that pouch-like heart muscle constructs can be generated by using a novel EHT-casting technology and applied as heart-embracing cardiac grafts in vivo. Methods and Results - Pouch-like EHTs (inner/outer diameter: 10/12 mm) can be generated mainly from neonatal rat heart cells, collagen type I, and serum containing culture medium. They contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. First implantation studies indicate that pouch-like EHTs can be slipped over uninjured adult rat hearts to completely cover the left and right ventricles. Fourteen days after implantation, EHT-grafts stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived. Conclusions - Pouch-like EHTs can be generated with structural and functional properties of native myocardium. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo."],["dc.identifier.doi","10.1161/CIRCULATIONAHA.106.679688"],["dc.identifier.gro","3143439"],["dc.identifier.isi","000249364500003"],["dc.identifier.pmid","17846298"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/953"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","79th Annual Scientific Session of the American-Heart-Association"],["dc.relation.eventlocation","Chicago, IL"],["dc.relation.ispartof","Circulation"],["dc.relation.issn","0009-7322"],["dc.title","Development of a biological ventricular assist device - Preliminary data from a small animal model"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1285"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","1298"],["dc.bibliographiccitation.volume","123"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Christalla, Peter"],["dc.contributor.author","Rubart, Michael"],["dc.contributor.author","Muppala, Vijayakumar"],["dc.contributor.author","Doeker, Stephan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Rau, Thomas"],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Schwoerer, Alexander Peter"],["dc.contributor.author","Ehmke, Heimo"],["dc.contributor.author","Schumacher, Udo"],["dc.contributor.author","Fuchs, Sigrid"],["dc.contributor.author","Lange, Claudia"],["dc.contributor.author","Becker, Alexander"],["dc.contributor.author","Tao, Wen"],["dc.contributor.author","Scherschel, John A."],["dc.contributor.author","Soonpaa, Mark H."],["dc.contributor.author","Yang, Tao"],["dc.contributor.author","Lin, Qiong"],["dc.contributor.author","Zenke, Martin"],["dc.contributor.author","Han, Dong-Wook"],["dc.contributor.author","Schoeler, Hans R."],["dc.contributor.author","Rudolph, Cornelia"],["dc.contributor.author","Steinemann, Doris"],["dc.contributor.author","Schlegelberger, Brigitte"],["dc.contributor.author","Kattman, Steve"],["dc.contributor.author","Witty, Alec"],["dc.contributor.author","Keller, Gordon"],["dc.contributor.author","Field, Loren J."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2017-09-07T11:47:47Z"],["dc.date.available","2017-09-07T11:47:47Z"],["dc.date.issued","2013"],["dc.description.abstract","Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair."],["dc.identifier.doi","10.1172/JCI66854"],["dc.identifier.gro","3142382"],["dc.identifier.isi","000315749400038"],["dc.identifier.pmid","23434590"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7663"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/10"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.issn","0021-9738"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.title","Parthenogenetic stem cells for tissue-engineered heart repair"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","464"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","474"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Münzel, Felix"],["dc.contributor.author","Muhlhauser, U."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Schneiderbanger, Karin"],["dc.contributor.author","Schubert, Pia"],["dc.contributor.author","Engmann, S."],["dc.contributor.author","Eschenhagen, Thomas"],["dc.contributor.author","Zolk, O"],["dc.date.accessioned","2017-09-07T11:53:38Z"],["dc.date.available","2017-09-07T11:53:38Z"],["dc.date.issued","2005"],["dc.description.abstract","Objective: The mitogen-activated kinase kinases (MEK)-extracellular signal-regulated kinases (ERK) signaling pathway is activated by agonists like catecholamines or endothelin-1 (ET-1) and has been implicated in cardiac pathology, such as the progression from cardiac hypertrophy to failure. The purpose of the present study, performed in an in vitro model of contractile failure, was to evaluate whether MEK inhibition prevents functional deterioration. Methods and results: Contractile dysfunction was induced in reconstituted rat heart tissue by concomitant treatment with ET-1 (10 nmol/l) and isoprenaline (ISO, 10 nmol/l) for 5 days. While basal force of contraction was unchanged, contractile responsiveness to beta-adrenoceptor agonists was markedly impaired (active force declined to 51% of controls) and was associated with decreased lusitropy. Moreover, in ET-1 + ISO-treated heart tissues, reprogramming of gene expression was observed with an increased ratio of beta-myosin heavy chain (MHC) to alpha-MHC mRNA and increased transcript levels of ANF and skeletal/smooth Muscle alpha-actin isoforms. The MEK inhibitor U0126 (10 mu mol/l) almost completely prevented the reduction in p-adrenergic responsiveness and the negative lusitropic effect of ET-1+ISO co-stimulation. In addition, U0126 completely normalized ANF gene expression, but did not affect or only marginally affected expression of MHC and a-actin isoforms. Conclusions: These results suggest that interruption of the MEK-ERK signaling pathway with a specific MEK inhibitor prevents, in part, the occurrence of a pathologic phenotype secondary to excessive stimulation with neurotulmoral factors. The MEK-ERK pathway seems to be all important but not exclusive regulatory pathway responsible for the development of contractile dysfunction. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved."],["dc.identifier.doi","10.1016/j.cardiores.2005.06.020"],["dc.identifier.gro","3143781"],["dc.identifier.isi","000233469400017"],["dc.identifier.pmid","16040022"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1332"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0008-6363"],["dc.title","Endothelin-1 and isoprenaline co-stimulation causes contractile failure which is partially reversed by MEK inhibition"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]