File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium

TitleProarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium
Authors
KeywordsCardiomyocytes
Embryonic stem cells
Myocardial infarction
Proarrhythmias
Issue Date2010
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/heartrhythmjournal
Citation
Heart Rhythm, 2010, v. 7 n. 12, p. 1852-1859 How to Cite?
AbstractBackground Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of postmyocardial infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear. Objective The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI. Methods We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10 5 undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation. Results In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P <.05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P <.05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P <.05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P <.05) compared with in the MI group (2,042 ± 406 mmHg/s). Conclusions Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs. © 2010 Heart Rhythm Society.
Persistent Identifierhttp://hdl.handle.net/10722/124962
ISSN
2015 Impact Factor: 4.391
2015 SCImago Journal Rankings: 2.756
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7594/05M
HKU 7769/08M
National Institutes of HealthR01 HL72857
Hong Kong Research Grant CouncilHKU 8/CRF/09
Funding Information:

This study was supported by the Research Grants Council of Hong Kong, General Research Fund (nos. HKU 7594/05M, HKU 7769/08M), Outstanding Researcher Award 2007-2008 (to HFT), the National Institutes of Health (no. R01 HL72857 to RAL), and Collaborative Research Fund of Hong Kong Research Grant Council (HKU 8/CRF/09). The first two authors contributed equally to this work.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLiao, SYen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorSiu, CWen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorLai, WHen_HK
dc.contributor.authorAu, KWen_HK
dc.contributor.authorLee, YKen_HK
dc.contributor.authorChan, YCen_HK
dc.contributor.authorYip, PMCen_HK
dc.contributor.authorWu, EXen_HK
dc.contributor.authorWu, Yen_HK
dc.contributor.authorLau, CPen_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorTse, HFen_HK
dc.date.accessioned2010-10-31T11:03:50Z-
dc.date.available2010-10-31T11:03:50Z-
dc.date.issued2010en_HK
dc.identifier.citationHeart Rhythm, 2010, v. 7 n. 12, p. 1852-1859en_HK
dc.identifier.issn1547-5271en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124962-
dc.description.abstractBackground Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of postmyocardial infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear. Objective The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI. Methods We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10 5 undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation. Results In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P <.05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P <.05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P <.05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P <.05) compared with in the MI group (2,042 ± 406 mmHg/s). Conclusions Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs. © 2010 Heart Rhythm Society.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/heartrhythmjournalen_HK
dc.relation.ispartofHeart Rhythmen_HK
dc.subjectCardiomyocytesen_HK
dc.subjectEmbryonic stem cellsen_HK
dc.subjectMyocardial infarctionen_HK
dc.subjectProarrhythmiasen_HK
dc.subject.meshArrhythmias, Cardiac - etiology-
dc.subject.meshEmbryonic Stem Cells - transplantation-
dc.subject.meshMyocytes, Cardiac - transplantation-
dc.subject.meshStem Cell Transplantation - adverse effects-
dc.titleProarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardiumen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1547-5271&volume=7&issue=12&spage=1852&epage=1859&date=2010&atitle=Proarrhythmic+risk+of+embryonic+stem+cell-derived+cardiomyocyte+transplantation+in+infarcted+myocardium-
dc.identifier.emailSiu, CW:cwdsiu@hkucc.hku.hken_HK
dc.identifier.emailChan, YC:yauchi@graduate.hku.hken_HK
dc.identifier.emailWu, EX:ewu1@hkucc.hku.hken_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityWu, EX=rp00193en_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.hrthm.2010.09.006en_HK
dc.identifier.pmid20833268-
dc.identifier.scopuseid_2-s2.0-78650085892en_HK
dc.identifier.hkuros182832en_HK
dc.identifier.hkuros191348-
dc.identifier.hkuros239712-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650085892&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1852en_HK
dc.identifier.epage1859en_HK
dc.identifier.isiWOS:000284875500030-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectEmbryonic stem cell transplantation as a novel therapy for post-infarct left ventricular remodeling-
dc.relation.projectPluripotent Human Stem Cell Platform for Tissue Regeneration and Drug Screening for Cardiovascular Diseases-
dc.identifier.scopusauthoridLiao, SY=22433820700en_HK
dc.identifier.scopusauthoridLiu, Y=36196696200en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK
dc.identifier.scopusauthoridZhang, Y=35785466900en_HK
dc.identifier.scopusauthoridLai, WH=18434390500en_HK
dc.identifier.scopusauthoridAu, KW=9738204200en_HK
dc.identifier.scopusauthoridLee, YK=25958641200en_HK
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridYip, PMC=36741033300en_HK
dc.identifier.scopusauthoridWu, EX=7202128034en_HK
dc.identifier.scopusauthoridWu, Y=37099170600en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.customcontrol.immutablejt 130822-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats