Hübscher, Daniela

[["dc.bibliographiccitation.firstpage","975"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","991"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Guessoum, Celina I."],["dc.contributor.author","Lam, Tuan-Dinh D."],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Schellinger, Isabel N."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Huber, Mia A."],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Raaz, Uwe"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lüscher, Thomas F."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2018-04-23T11:48:11Z"],["dc.date.available","2018-04-23T11:48:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype."],["dc.identifier.doi","10.1016/j.jacc.2017.06.061"],["dc.identifier.gro","3142333"],["dc.identifier.pmid","28818208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13468"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/204"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Wollnik"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Haupt, Luis Peter"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Maus, Andreas"],["dc.contributor.author","Köhne, Steffen"],["dc.contributor.author","Tappu, Rewati"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2022-04-01T10:01:09Z"],["dc.date.available","2022-04-01T10:01:09Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20 + B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca 2+ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca 2+ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients."],["dc.identifier.doi","10.1007/s00395-022-00918-7"],["dc.identifier.pii","918"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105613"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Human Gene Therapy"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Wolf, F."],["dc.contributor.author","Becker, A."],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Huebscher, Daniela"],["dc.contributor.author","Field, Loren J."],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Guan, Kaomei"],["dc.date.accessioned","2018-11-07T11:22:43Z"],["dc.date.available","2018-11-07T11:22:43Z"],["dc.date.issued","2009"],["dc.format.extent","1406"],["dc.identifier.isi","000271441000171"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56035"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mary Ann Liebert Inc"],["dc.publisher.place","New rochelle"],["dc.relation.conference","Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research"],["dc.relation.eventlocation","Hannover, GERMANY"],["dc.relation.issn","1043-0342"],["dc.title","Characterization and maintenance of adult spermatogonial stem cell culture"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Human Gene Therapy"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Jende, Joerg"],["dc.contributor.author","Huebscher, Daniela"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Guan, Kaomei"],["dc.date.accessioned","2018-11-07T11:22:44Z"],["dc.date.available","2018-11-07T11:22:44Z"],["dc.date.issued","2009"],["dc.format.extent","1484"],["dc.identifier.isi","000271441000385"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56038"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mary Ann Liebert Inc"],["dc.publisher.place","New rochelle"],["dc.relation.conference","Combined Meeting of the 17th European-Society-of-Gene-and-Cell-Therapy/16th German-Society-for-Gene-Therapy/4th German-Society-for-Stem-Cell-Research"],["dc.relation.eventlocation","Hannover, GERMANY"],["dc.relation.issn","1043-0342"],["dc.title","Generation of hepatic-like cells from multipotent adult mouse germline stem cells"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","806"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.lastpage","819"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Balleininger, Martina"],["dc.contributor.author","Vaz, Frederic M."],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Vukotic, Milena"],["dc.contributor.author","Wanders, Ronald J. A."],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Guan, Kaomei"],["dc.date.accessioned","2017-09-07T11:47:37Z"],["dc.date.available","2017-09-07T11:47:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Barth syndrome (BTHS) patients carrying mutations in tafazzin (TAZ1), which is involved in the final maturation of cardiolipin, present with dilated cardiomyopathy, skeletal myopathy, growth retardation and neutropenia. To study how mitochondrial function is impaired in BTHS patients, we generated induced pluripotent stem cells (iPSCs) to develop a novel and relevant human model system for BTHS. BTHS-iPSCs generated from dermal fibroblasts of three patients with different mutations in TAZ1 expressed pluripotency markers, and were able to differentiate into cells derived from all three germ layers both in vitro and in vivo. We used these cells to study the impact of tafazzin deficiency on mitochondria( oxidative phosphorylation. We found an impaired remodeling of cardiolipin, a dramatic decrease in basal oxygen consumption rate and in the maximal respiratory capacity in BTHS-iPSCs. Simultaneous measurement of extra-cellular acidification rate allowed us a thorough assessment of the metabolic deficiency in BTHS patients. Blue native gel analyses revealed that decreased respiration coincided with dramatic structural changes in respiratory chain supercomplexes leading to a massive increase in generation of reactive oxygen species. Our data demonstrate that BTHS-iPSCs are capable of modeling BTHS by recapitulating the disease phenotype and thus are important tools for studying the disease mechanism. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.scr.2013.05.005"],["dc.identifier.gro","3142297"],["dc.identifier.isi","000323586600012"],["dc.identifier.pmid","23792436"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11333"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6720"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/12"],["dc.language.iso","en"],["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","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A04: Patienten-spezifische induzierte pluripotente Stammzellen zur funktionellen Untersuchung von Ryanodinrezeptor-Mutationen"],["dc.relation","SFB 1002 | A06: Molekulare Grundlagen mitochondrialer Kardiomyopathien"],["dc.relation.issn","1873-5061"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","207"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Vascular Research"],["dc.bibliographiccitation.lastpage","220"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Kaiser, Diana"],["dc.contributor.author","Huebscher, Daniela"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:43:10Z"],["dc.date.available","2017-09-07T11:43:10Z"],["dc.date.issued","2012"],["dc.description.abstract","Pluripotent stem cells hold great promise for the treatment of cardiovascular disease. We previously described multipotent adult germline stem cells (maGSCs) from mouse testis with differentiation potential similar to embryonic stem cells. The aim of this work was to differentiate maGSCs into functional endothelial cells and to study their potential for vasculogenesis. MaGSCs were cocultivated with OP9 stromal cells to induce differentiation into cardiovascular progenitors, i.e. fetal liver kinase 1-positive (Flk-1(+)) cells. Five days later, Flk-1(+) cells were separated using fluorescence-activated cell sorting, followed by cultivation on collagen type IV under endothelial differentiation conditions. At different time points, maGSC-derived endothelial-like cells were characterized using RT-PCR, flow cytometry, immunofluorescence and functional assays. Cultivation of Flk-1(+) cells resulted in the progressive upregulation of endothelial cell markers, including VE-cadherin, von Willebrand factor and endothelial nitric oxide synthase. Moreover, Flk-1(+) maGSC-derived endothelial-like cells were able to branch and form networks in vitro and promoted functional blood vessel formation in vivo. Importantly, Flk-1(+) cells retained their potential to proliferate and could be continuously expanded, while the ability of contact inhibition was preserved. Thus, maGSCs may provide a useful source of endothelial-like cells to study the basic mechanisms of vasculogenesis or endothelial differentiation. Copyright 2012S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000332910"],["dc.identifier.gro","3142600"],["dc.identifier.isi","000303967900003"],["dc.identifier.pmid","22433575"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22"],["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","1018-1172"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Differentiation of Multipotent Adult Germ line Stem Cells Derived from Mouse Testis into Functional Endothelial Cells"],["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","1304"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","1311"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Perera, Ruwan K."],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Steinbrecher, Julia H."],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Abesser, Marco"],["dc.contributor.author","Schuh, Kai"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.date.accessioned","2018-05-07T11:53:29Z"],["dc.date.available","2018-05-07T11:53:29Z"],["dc.date.issued","2015"],["dc.description.abstract","Cyclic nucleotides are second messengers that regulate cardiomyocyte function through compartmentalized signaling in discrete subcellular microdomains. However, the role of different microdomains and their changes in cardiac disease are not well understood."],["dc.identifier.doi","10.1161/CIRCRESAHA.116.306082"],["dc.identifier.pmid","25688144"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14623"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/82"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.doi","10.1161/CIRCRESAHA.116.306082"],["dc.relation.eissn","1524-4571"],["dc.relation.issn","1524-4571"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.title","Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-induced augmentation of β-adrenoceptor-stimulated contractility in early cardiac hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","101746"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2020-12-10T15:21:15Z"],["dc.date.available","2020-12-10T15:21:15Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.scr.2020.101746"],["dc.identifier.issn","1873-5061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72964"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Generation of iPSC-lines from two independent Takotsubo syndrome patients with recurrent Takotsubo events"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","343"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","HLA"],["dc.bibliographiccitation.lastpage","344"],["dc.bibliographiccitation.volume","89"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Huebscher, Daniela"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Stauske, Michael"],["dc.contributor.author","Hejazi, Maryam"],["dc.contributor.author","Uhrberg, Markus"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.date.accessioned","2018-11-07T10:23:29Z"],["dc.date.available","2018-11-07T10:23:29Z"],["dc.date.issued","2017"],["dc.identifier.isi","000400973300013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42464"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.publisher.place","Hoboken"],["dc.relation.issn","2059-2310"],["dc.relation.issn","2059-2302"],["dc.title","HUMAN CARDIOMYOCYTES DERIVED FROM INDUCED PLURIPOTENT STEM CELLS ARE TARGETS FOR ACTIVATED AUTOLOGOUS AND ALLOGENEIC NATURAL KILLER CELLS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","67"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Huebscher, Daniela"],["dc.contributor.author","Kaiser, Diana"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Guan, Kaomei"],["dc.date.accessioned","2018-11-07T10:27:34Z"],["dc.date.available","2018-11-07T10:27:34Z"],["dc.date.issued","2017"],["dc.description.abstract","Transplantation of stem cells represents an upcoming therapy for many degenerative diseases. For clinical use, transplantation of pluripotent stem cell-derived cells should lead to integration of functional grafts without immune rejection or teratoma formation. Our previous studies showed that the risk of teratoma formation is highly influenced by the immune system of the recipients. In this study, we have observed a higher teratoma formation rate when undifferentiated so-called multipotent adult germline stem cells (maGSCs) were transplanted into the heart of T, B, and natural killer (NK) cell-deficient RAG2(-/-)gamma c(-/-) mice than in RAG2(-/-) mice, which still have NK cells. Notably, in both strains, the teratoma formation rate was significantly reduced by the immunosuppressive drug cyclosporine A (CsA). Thus, CsA had a profound effect on teratoma formation independent of its immunosuppressive effects. The transplantation into RAG2(-/-) mice led to an activation of NK cells, which reached the maximum 14 days after transplantation and was not affected by CsA. The in vivo-activated NK cells efficiently killed YAC-1 and also maGSC target cells. This NK cell activation was confirmed in C57BL/6 wild-type mice whether treated with CsA or not. Sham operations in wild-type mice indicated that the inflammatory response to open heart surgery rather than the transplantation of maGSCs activated the NK cell system. An activation of NK cells during the transplantation of stem cell-derived in vitro differentiated grafts might be clinically beneficial by reducing the risk of teratoma formation by residual pluripotent cells."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.3389/fimmu.2017.00067"],["dc.identifier.isi","000393436700001"],["dc.identifier.pmid","28220117"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14269"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43258"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/206"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","1664-3224"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Tumorigenicity of Multipotent Adult Germline Stem Cells Transplanted into the Heart Is Affected by Natural Killer Cells and by Cyclosporine A Independent of Its Immunosuppressive Effects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]