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Article: Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: Insights into the development of cell-based pacemakers

TitleFunctional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: Insights into the development of cell-based pacemakers
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2005
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
Citation
Circulation, 2005, v. 111 n. 1, p. 11-20 How to Cite?
AbstractBackground - Human embryonic stem cells (hESCs) derived from blastocysts can propagate indefinitely in culture while maintaining pluripotency, including the ability to differentiate into cardiomyocytes (CMs); therefore, hESCs may provide an unlimited source of human CMs for cell-based therapies. Although CMs can be derived from hESCs ex vivo, it remains uncertain whether a functional syncytium can be formed between donor and recipient cells after engraftment. Methods and Results - Using a combination of electrophysiological and imaging techniques, here we demonstrate that electrically active, donor CMs derived from hESCs that had been stably genetically engineered by a recombinant lentivirus can functionally integrate with otherwise-quiescent, recipient, ventricular CMs to induce rhythmic electrical and contractile activities in vitro. The integrated syncytium was responsive to the β-adrenergic agonist isoproterenol as well as to other pharmacological agents such as lidocaine and ZD7288. Similarly, a functional hESC-derived pacemaker could be implanted in the left ventricle in vivo. Detailed optical mapping of the epicardial surface of guinea pig hearts transplanted with hESC-derived CMs confirmed the successful spread of membrane depolarization from the site of injection to the surrounding myocardium. Conclusions - We conclude that electrically active, hESC-derived CMs are capable of actively pacing quiescent, recipient, ventricular CMs in vitro and ventricular myocardium in vivo. Our results may lead to an alternative or a supplemental method for correcting defects in cardiac impulse generation, such as cell-based pacemakers.
Persistent Identifierhttp://hdl.handle.net/10722/91634
ISSN
2015 Impact Factor: 17.047
2015 SCImago Journal Rankings: 7.853
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXue, Ten_HK
dc.contributor.authorCho, HCen_HK
dc.contributor.authorAkar, FGen_HK
dc.contributor.authorTsang, SYen_HK
dc.contributor.authorJones, SPen_HK
dc.contributor.authorMarbán, Een_HK
dc.contributor.authorTomaselli, GFen_HK
dc.contributor.authorLi, RAen_HK
dc.date.accessioned2010-09-17T10:22:32Z-
dc.date.available2010-09-17T10:22:32Z-
dc.date.issued2005en_HK
dc.identifier.citationCirculation, 2005, v. 111 n. 1, p. 11-20en_HK
dc.identifier.issn0009-7322en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91634-
dc.description.abstractBackground - Human embryonic stem cells (hESCs) derived from blastocysts can propagate indefinitely in culture while maintaining pluripotency, including the ability to differentiate into cardiomyocytes (CMs); therefore, hESCs may provide an unlimited source of human CMs for cell-based therapies. Although CMs can be derived from hESCs ex vivo, it remains uncertain whether a functional syncytium can be formed between donor and recipient cells after engraftment. Methods and Results - Using a combination of electrophysiological and imaging techniques, here we demonstrate that electrically active, donor CMs derived from hESCs that had been stably genetically engineered by a recombinant lentivirus can functionally integrate with otherwise-quiescent, recipient, ventricular CMs to induce rhythmic electrical and contractile activities in vitro. The integrated syncytium was responsive to the β-adrenergic agonist isoproterenol as well as to other pharmacological agents such as lidocaine and ZD7288. Similarly, a functional hESC-derived pacemaker could be implanted in the left ventricle in vivo. Detailed optical mapping of the epicardial surface of guinea pig hearts transplanted with hESC-derived CMs confirmed the successful spread of membrane depolarization from the site of injection to the surrounding myocardium. Conclusions - We conclude that electrically active, hESC-derived CMs are capable of actively pacing quiescent, recipient, ventricular CMs in vitro and ventricular myocardium in vivo. Our results may lead to an alternative or a supplemental method for correcting defects in cardiac impulse generation, such as cell-based pacemakers.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.orgen_HK
dc.relation.ispartofCirculationen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAction Potentialsen_HK
dc.subject.meshAdrenergic beta-Agonists - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Fusionen_HK
dc.subject.meshCells, Cultured - cytology - physiologyen_HK
dc.subject.meshDefective Viruses - genetics - physiologyen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenes, Reporteren_HK
dc.subject.meshGenetic Vectors - pharmacologyen_HK
dc.subject.meshGiant Cells - cytology - drug effectsen_HK
dc.subject.meshGreen Fluorescent Proteins - analysis - geneticsen_HK
dc.subject.meshGuinea Pigsen_HK
dc.subject.meshHIV-1 - genetics - physiologyen_HK
dc.subject.meshHeart - physiologyen_HK
dc.subject.meshHeart Conduction System - cytology - physiologyen_HK
dc.subject.meshHeart Ventricles - cytologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIsoproterenol - pharmacologyen_HK
dc.subject.meshLidocaine - pharmacologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMyocardial Contraction - drug effectsen_HK
dc.subject.meshMyocytes, Cardiac - cytology - drug effects - physiology - transplantationen_HK
dc.subject.meshOrgan Culture Techniquesen_HK
dc.subject.meshPericardium - physiologyen_HK
dc.subject.meshPluripotent Stem Cells - cytology - physiologyen_HK
dc.subject.meshPyrimidines - pharmacologyen_HK
dc.subject.meshRatsen_HK
dc.subject.meshTransduction, Geneticen_HK
dc.titleFunctional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: Insights into the development of cell-based pacemakersen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1161/01.CIR.0000151313.18547.A2en_HK
dc.identifier.pmid15611367-
dc.identifier.scopuseid_2-s2.0-11244249952en_HK
dc.identifier.hkuros183072-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-11244249952&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume111en_HK
dc.identifier.issue1en_HK
dc.identifier.spage11en_HK
dc.identifier.epage20en_HK
dc.identifier.isiWOS:000226065300004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridXue, T=7005064190en_HK
dc.identifier.scopusauthoridCho, HC=8559571900en_HK
dc.identifier.scopusauthoridAkar, FG=6701446552en_HK
dc.identifier.scopusauthoridTsang, SY=7102255908en_HK
dc.identifier.scopusauthoridJones, SP=7405932019en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK
dc.identifier.scopusauthoridTomaselli, GF=7005223451en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK

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