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dc.contributor.authorTreskes, Philipp
dc.contributor.authorNeef, Klaus
dc.contributor.authorSrinivasan, Sureshkumar Perumal
dc.contributor.authorHalbach, Marcel
dc.contributor.authorStamm, Christof
dc.contributor.authorCowan, Douglas Burr
dc.contributor.authorScherner, Maximilian
dc.contributor.authorMadershahian, Navid
dc.contributor.authorWittwer, Thorsten
dc.contributor.authorHescheler, Jürgen
dc.contributor.authorWahlers, Thorsten
dc.contributor.authorChoi, Yeong-Hoon
dc.date.accessioned2018-04-10T20:43:59Z
dc.date.issued2015
dc.identifierQuick submit: 2015-02-06T09:44:58-05:00
dc.identifier.citationTreskes, Philipp, Klaus Neef, Sureshkumar Perumal Srinivasan, Marcel Halbach, Christof Stamm, Douglas Cowan, Maximilian Scherner, et al. 2015. “Preconditioning of Skeletal Myoblast-Based Engineered Tissue Constructs Enables Functional Coupling to Myocardium in Vivo.” The Journal of Thoracic and Cardiovascular Surgery 149 (1) (January): 348–356. doi:10.1016/j.jtcvs.2014.09.034.en_US
dc.identifier.issn0022-5223en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35442698
dc.description.abstractObjective Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication. Methods Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 week after transplantation. Results Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses of the maximum stimulation frequency (5.65 ± 0.37 Hz), conduction velocity (0.087 ± 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 ± 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 ± 0.238 Hz, P < .001; conduction velocity, 0.300 ± 0.057 m/s, P < .01; conduction block, 1.983 ± 0.077 mM 1-heptanol, P < .001). Conclusions Although untreated skeletal myoblasts cannot couple to cardiomyocytes, we confirm that mechanical preconditioning enables transplanted skeletal myoblasts to functionally interact with cardiomyocytes in vivo and, thus, reinvigorate the concept of skeletal myoblast-based cardiac cell therapy.en_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.jtcvs.2014.09.034en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/25439779en_US
dash.licenseOAP
dc.titlePreconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivoen_US
dc.typeJournal Articleen_US
dc.date.updated2015-02-06T14:44:58Z
dc.description.versionAccepted Manuscripten_US
dc.rights.holderTreskes P, Neef K, Srinivasan SP, Halbach M, Stamm C, Cowan D, Scherner M, Madershahian N, Wittwer T, Hescheler J, Wahlers T, Choi YH.
dc.relation.journalThe Journal of Thoracic and Cardiovascular Surgeryen_US
dash.depositing.authorCowan, Douglas Burr
dc.date.available2018-04-10T20:43:59Z
dc.identifier.doi10.1016/j.jtcvs.2014.09.034*
dash.authorsorderedfalse
dash.contributor.affiliatedCowan, Douglas


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