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Article: Calcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

TitleCalcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors
KeywordsCalcium handling
Cardiomyocytes
Human induced pluripotent stem cells
Issue Date2011
PublisherHumana Press, Inc. The Journal's web site is located at http://www.springer.com/humana+press/molecular%2C+cell+and+stem+cell+biology/journal/12015
Citation
Stem Cell Reviews And Reports, 2011, v. 7 n. 4, p. 976-986 How to Cite?
AbstractRationale: Cardiomyocytes generated from human induced pluripotent stem cells (hiPSCs) are suggested as the most promising candidate to replenish cardiomyocyte loss in regenerative medicine. Little is known about their calcium homeostasis, the key process underlying excitation-contraction coupling. Objective: We investigated the calcium handling properties of hiPSC-derived cardiomyocytes and compared with those from human embryonic stem cells (hESCs). Methods and Results: We differentiated cardiomyocytes from hiPSCs (IMR90 and KS1) and hESCs (H7 and HES3) with established protocols. Beating outgrowths from embryoid bodies were typically observed 2 weeks after induction. Cells in these outgrowths were stained positively for tropomyosin and sarcomeric alpha-actinin. Reverse-transcription polymerase chain reaction studies demonstrated the expressions of cardiac-specific markers in both hiPSC- and hESC-derived cardiomyocytes. Calcium handling properties of 20-day-old hiPSC- and hESC-derived cardiomyocytes were investigated using fluorescence confocal microscopy. Compared with hESC-derived cardiomyocytes, spontaneous calcium transients from both lines of hiPSC-derived cardiomyocytes were of significantly smaller amplitude and with slower maximal upstroke velocity. Better caffeine-induced calcium handling kinetics in hESC-CMs indicates a higher sacroplasmic recticulum calcium store. Furthermore, in contrast with hESC-derived cardiomyocytes, ryanodine did not reduce the amplitudes, maximal upstroke and decay velocity of calcium transients of hiPSC-derived cardiomyocytes. In addition, spatial inhomogeneity in temporal properties of calcium transients across the width of cardiomyocytes was more pronounced in hiPSC-derived cardiomyocytes than their hESC counterpart as revealed line-scan calcium imaging. Expressions of the key calcium-handling proteins including ryanodine recptor-2 (RyR2), sacroplasmic recticulum calcium-ATPase (SERCA), junction (Jun) and triadin (TRDN), were significantly lower in hiPSC than in hESCs. Conclusions: The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts. © 2011 The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/134666
ISSN
2018 Impact Factor: 4.697
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, YKen_HK
dc.contributor.authorNg, KMen_HK
dc.contributor.authorLai, WHen_HK
dc.contributor.authorChan, YCen_HK
dc.contributor.authorLau, YMen_HK
dc.contributor.authorLian, Qen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorSiu, CWen_HK
dc.date.accessioned2011-07-05T08:23:52Z-
dc.date.available2011-07-05T08:23:52Z-
dc.date.issued2011en_HK
dc.identifier.citationStem Cell Reviews And Reports, 2011, v. 7 n. 4, p. 976-986en_HK
dc.identifier.issn1550-8943en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134666-
dc.description.abstractRationale: Cardiomyocytes generated from human induced pluripotent stem cells (hiPSCs) are suggested as the most promising candidate to replenish cardiomyocyte loss in regenerative medicine. Little is known about their calcium homeostasis, the key process underlying excitation-contraction coupling. Objective: We investigated the calcium handling properties of hiPSC-derived cardiomyocytes and compared with those from human embryonic stem cells (hESCs). Methods and Results: We differentiated cardiomyocytes from hiPSCs (IMR90 and KS1) and hESCs (H7 and HES3) with established protocols. Beating outgrowths from embryoid bodies were typically observed 2 weeks after induction. Cells in these outgrowths were stained positively for tropomyosin and sarcomeric alpha-actinin. Reverse-transcription polymerase chain reaction studies demonstrated the expressions of cardiac-specific markers in both hiPSC- and hESC-derived cardiomyocytes. Calcium handling properties of 20-day-old hiPSC- and hESC-derived cardiomyocytes were investigated using fluorescence confocal microscopy. Compared with hESC-derived cardiomyocytes, spontaneous calcium transients from both lines of hiPSC-derived cardiomyocytes were of significantly smaller amplitude and with slower maximal upstroke velocity. Better caffeine-induced calcium handling kinetics in hESC-CMs indicates a higher sacroplasmic recticulum calcium store. Furthermore, in contrast with hESC-derived cardiomyocytes, ryanodine did not reduce the amplitudes, maximal upstroke and decay velocity of calcium transients of hiPSC-derived cardiomyocytes. In addition, spatial inhomogeneity in temporal properties of calcium transients across the width of cardiomyocytes was more pronounced in hiPSC-derived cardiomyocytes than their hESC counterpart as revealed line-scan calcium imaging. Expressions of the key calcium-handling proteins including ryanodine recptor-2 (RyR2), sacroplasmic recticulum calcium-ATPase (SERCA), junction (Jun) and triadin (TRDN), were significantly lower in hiPSC than in hESCs. Conclusions: The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts. © 2011 The Author(s).en_HK
dc.languageengen_US
dc.publisherHumana Press, Inc. The Journal's web site is located at http://www.springer.com/humana+press/molecular%2C+cell+and+stem+cell+biology/journal/12015en_HK
dc.relation.ispartofStem Cell Reviews and Reportsen_HK
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.en_US
dc.subjectCalcium handlingen_HK
dc.subjectCardiomyocytesen_HK
dc.subjectHuman induced pluripotent stem cellsen_HK
dc.subject.meshCalcium - metabolism-
dc.subject.meshEmbryonic Stem Cells - cytology - metabolism-
dc.subject.meshHomeostasis-
dc.subject.meshInduced Pluripotent Stem Cells - cytology-
dc.subject.meshMyocytes, Cardiac - cytology/drug effects - metabolism-
dc.titleCalcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4551/resserv?sid=springerlink&genre=article&atitle=Calcium Homeostasis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes&title=Stem Cell Reviews and Reports&issn=15508943&date=2011-11-01&volume=7&issue=4& spage=976&authors=Yee-Ki Lee, Kwong-Man Ng, Wing-Hon Lai, <i>et al.</i>en_US
dc.identifier.emailNg, KM: skykmng@hkucc.hku.hken_HK
dc.identifier.emailChan, YC: ycchan09@hku.hken_HK
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hken_HK
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_HK
dc.identifier.emailSiu, CW: cwdsiu@hkucc.hku.hken_HK
dc.identifier.authorityNg, KM=rp01670en_HK
dc.identifier.authorityChan, YC=rp01502en_HK
dc.identifier.authorityLian, Q=rp00267en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.identifier.authoritySiu, CW=rp00534en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s12015-011-9273-3en_HK
dc.identifier.pmid21614516-
dc.identifier.pmcidPMC3226695-
dc.identifier.scopuseid_2-s2.0-82355168775en_HK
dc.identifier.hkuros185835-
dc.identifier.hkuros200848-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82355168775&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue4en_HK
dc.identifier.spage976en_HK
dc.identifier.epage986en_HK
dc.identifier.eissn1558-6804en_US
dc.identifier.isiWOS:000297597800019-
dc.publisher.placeUnited Statesen_HK
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.identifier.scopusauthoridLee, YK=25958641200en_HK
dc.identifier.scopusauthoridNg, KM=25122990200en_HK
dc.identifier.scopusauthoridLai, WH=18434390500en_HK
dc.identifier.scopusauthoridChan, YC=7403676116en_HK
dc.identifier.scopusauthoridLau, YM=35102601300en_HK
dc.identifier.scopusauthoridLian, Q=7003399023en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridSiu, CW=7006550690en_HK
dc.identifier.citeulike9402203-
dc.identifier.issnl1550-8943-

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