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Article: Functional sarcoplasmic reticulum for calcium handling of human embryonic stem cell-derived cardiomyocytes: Insights for driven maturation

TitleFunctional sarcoplasmic reticulum for calcium handling of human embryonic stem cell-derived cardiomyocytes: Insights for driven maturation
Authors
KeywordsCa2+ handling
Cardiomyocytes
Human embryonic stem cells
Maturation
Sarcoplasmic reticulum
Issue Date2007
PublisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.com
Citation
Stem Cells, 2007, v. 25 n. 12, p. 3038-3044 How to Cite?
AbstractCardiomyocytes (CMs) are nonregenerative. Self-renewable pluripotent human embryonic stem cells (hESCs) can differentiate into CMs for cell-based therapies. In adult CMs, Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR) is key in excitation-contraction coupling. Therefore, proper Ca2+ handling properties of hESC-derived CMs are required for their successful functional integration with the recipient heart. Here, we performed a comprehensive analysis of CMs differentiated from the H1 (H1-CMs) and HES2 (HES2-CMs) hESC lines and human fetal (F) and adult (A) left ventricular (LV) CMs. Upon electrical stimulation, all of H1-, HES2-, and FLV-CMs generated similar Ca 2+ transients. Caffeine induced Ca2+ release in 65% of FLV-CMs and ∼38% of H1- and HES2-CMs. Ryanodine significantly reduced the electrically evoked Ca2+ transient amplitudes of caffeine-responsive but not -insensitive HES2-and H1-CMs and slowed their upstroke; thapsigargin, which inhibits the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump, reduced the amplitude of only caffeine-responsive HES2- and H1-CMs and slowed the decay. SERCA2a expression was highest in ALV-CMs but comparable among H1-, HES2-, and FLV-CMs. The Na+-Ca2+ exchanger was substantially expressed in both HES2- and H1-CMs relative to FLV- and ALV-CMs. RyR was expressed in HES2-, H1-, and FLV-CMs, but the organized pattern for ALV-CMs was not observed. The regulatory proteins junctin, triadin, and calsequestrin were expressed in ALV-CMs but not HES2- and H1-CMs. We conclude that functional SRs are indeed expressed in hESC-CMs, albeit immaturely. Our results may lead to driven maturation of Ca2+ handling properties of hESCCMs for enhanced contractile functions. ©AlphaMed Press.
Persistent Identifierhttp://hdl.handle.net/10722/124902
ISSN
2015 Impact Factor: 5.902
2015 SCImago Journal Rankings: 3.438
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorJi, DFen_HK
dc.contributor.authorChung, WSen_HK
dc.contributor.authorLi, RAen_HK
dc.date.accessioned2010-10-31T11:00:34Z-
dc.date.available2010-10-31T11:00:34Z-
dc.date.issued2007en_HK
dc.identifier.citationStem Cells, 2007, v. 25 n. 12, p. 3038-3044en_HK
dc.identifier.issn1066-5099en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124902-
dc.description.abstractCardiomyocytes (CMs) are nonregenerative. Self-renewable pluripotent human embryonic stem cells (hESCs) can differentiate into CMs for cell-based therapies. In adult CMs, Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR) is key in excitation-contraction coupling. Therefore, proper Ca2+ handling properties of hESC-derived CMs are required for their successful functional integration with the recipient heart. Here, we performed a comprehensive analysis of CMs differentiated from the H1 (H1-CMs) and HES2 (HES2-CMs) hESC lines and human fetal (F) and adult (A) left ventricular (LV) CMs. Upon electrical stimulation, all of H1-, HES2-, and FLV-CMs generated similar Ca 2+ transients. Caffeine induced Ca2+ release in 65% of FLV-CMs and ∼38% of H1- and HES2-CMs. Ryanodine significantly reduced the electrically evoked Ca2+ transient amplitudes of caffeine-responsive but not -insensitive HES2-and H1-CMs and slowed their upstroke; thapsigargin, which inhibits the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump, reduced the amplitude of only caffeine-responsive HES2- and H1-CMs and slowed the decay. SERCA2a expression was highest in ALV-CMs but comparable among H1-, HES2-, and FLV-CMs. The Na+-Ca2+ exchanger was substantially expressed in both HES2- and H1-CMs relative to FLV- and ALV-CMs. RyR was expressed in HES2-, H1-, and FLV-CMs, but the organized pattern for ALV-CMs was not observed. The regulatory proteins junctin, triadin, and calsequestrin were expressed in ALV-CMs but not HES2- and H1-CMs. We conclude that functional SRs are indeed expressed in hESC-CMs, albeit immaturely. Our results may lead to driven maturation of Ca2+ handling properties of hESCCMs for enhanced contractile functions. ©AlphaMed Press.en_HK
dc.languageengen_HK
dc.publisherAlphaMed Press, Inc. The Journal's web site is located at http://www.stemcells.comen_HK
dc.relation.ispartofStem Cellsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCa2+ handlingen_HK
dc.subjectCardiomyocytesen_HK
dc.subjectHuman embryonic stem cellsen_HK
dc.subjectMaturationen_HK
dc.subjectSarcoplasmic reticulumen_HK
dc.subject.meshCalcium - metabolism-
dc.subject.meshCell Differentiation - drug effects - physiology-
dc.subject.meshEmbryonic Stem Cells - cytology - drug effects - physiology-
dc.subject.meshMyocytes, Cardiac - cytology - drug effects - physiology-
dc.subject.meshSarcoplasmic Reticulum - drug effects - physiology-
dc.titleFunctional sarcoplasmic reticulum for calcium handling of human embryonic stem cell-derived cardiomyocytes: Insights for driven maturationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1066-5099&volume=25&issue=12&spage=3038&epage=3044&date=2007&atitle=Functional+sarcoplasmic+reticulum+for+calcium+handling+of+human+embryonic+stem+cell-derived+cardiomyocytes:+insights+for+driven+maturation-
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1634/stemcells.2007-0549en_HK
dc.identifier.pmid17872499-
dc.identifier.scopuseid_2-s2.0-37349045754en_HK
dc.identifier.hkuros183045en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-37349045754&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue12en_HK
dc.identifier.spage3038en_HK
dc.identifier.epage3044en_HK
dc.identifier.eissn1549-4918-
dc.identifier.isiWOS:000251707200008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, J=24405638300en_HK
dc.identifier.scopusauthoridJi, DF=35082034500en_HK
dc.identifier.scopusauthoridChung, WS=35081808200en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK

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