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Book Chapter: Differentiation of embryonic stem cells into cardiomyocytes: role of ouabain

TitleDifferentiation of embryonic stem cells into cardiomyocytes: role of ouabain
Authors
KeywordsEmbryonic stem cells.
Issue Date2012
PublisherSpringer
Citation
Differentiation of embryonic stem cells into cardiomyocytes: role of ouabain. In Hayat, MA (Ed.), Stem cells and cancer stem cells, Volume 6, Therapeutic applications in disease and injury, p. 71-76. Dordrecht: Embryonic stem cells (ESCs) are able to differentiate into cardiac lineages and thus representing a promising source for cardiac regenerative therapy because of the self-renewal capacity. However, the therapeutic application of ESC-derived cardiomyocytes , 2012 How to Cite?
AbstractEmbryonic stem cells (ESCs) are able to differentiate into cardiac lineages and thus representing a promising source for cardiac regenerative therapy because of the self-renewal capacity. However, the therapeutic application of ESC-derived cardiomyocytes (ESC-CMCs) is limited by the low efficacy of the current protocols for cardiac differentiation and their immature phenotypes. With the clues of ouabain involving in physiological cardiac hypertrophic signalling pathway, our studies investigated the effects of such cardiotonic steroid on murine (m) ESCs cardiac differentiation. Differentiating mESCs in presence of ouabain yielded a significantly higher percentage of cardiomyocytes. Ouabain was also reported to inhibit Na+/K+-ATPase and followed with altered activity of the functionally coupled sodium-calcium exchanger (NCX-1). In our previous studies, the α1 and 2- isoforms of Na+/K+-ATPase, on which the cardiac predominant ouabain acts, were also increased in differentiated mESCs. Furthermore, among the three major MAPK cascades involved in hypertrophic response pathways, it was found that ouabain rescued the blockage of cardiac differentiation by the ERK1/2 pathway inhibitor, U0126. Interestingly, cardiomyocytes isolated from ouabain-treated mESCs exhibited more mature calcium handling kinetics. The higher amplitudes of caffeine-induced Ca2+ transient suggested a more mature sarcoplasmic recticulum (SR). Ouabain induced cardiac differentiation of mESC and maturation of mESC-CMCs probably via activation of ERK1/2. Further studies are necessary to investigate if ERK1/2 pathway plays a direct role in SR function that governing efficient calcium homeostasis of ESC-CMCs.
Persistent Identifierhttp://hdl.handle.net/10722/153354
ISBN

 

DC FieldValueLanguage
dc.contributor.authorLee, YKen_US
dc.contributor.authorNg, KMen_US
dc.contributor.authorLai, KWHen_US
dc.contributor.authorChan, YCen_US
dc.contributor.authorLau, VYMen_US
dc.contributor.authorTse, HFen_US
dc.contributor.authorSiu, DCWen_US
dc.date.accessioned2012-07-16T10:08:36Z-
dc.date.available2012-07-16T10:08:36Z-
dc.date.issued2012en_US
dc.identifier.citationDifferentiation of embryonic stem cells into cardiomyocytes: role of ouabain. In Hayat, MA (Ed.), Stem cells and cancer stem cells, Volume 6, Therapeutic applications in disease and injury, p. 71-76. Dordrecht: Embryonic stem cells (ESCs) are able to differentiate into cardiac lineages and thus representing a promising source for cardiac regenerative therapy because of the self-renewal capacity. However, the therapeutic application of ESC-derived cardiomyocytes , 2012en_US
dc.identifier.isbn9789400729926-
dc.identifier.urihttp://hdl.handle.net/10722/153354-
dc.description.abstractEmbryonic stem cells (ESCs) are able to differentiate into cardiac lineages and thus representing a promising source for cardiac regenerative therapy because of the self-renewal capacity. However, the therapeutic application of ESC-derived cardiomyocytes (ESC-CMCs) is limited by the low efficacy of the current protocols for cardiac differentiation and their immature phenotypes. With the clues of ouabain involving in physiological cardiac hypertrophic signalling pathway, our studies investigated the effects of such cardiotonic steroid on murine (m) ESCs cardiac differentiation. Differentiating mESCs in presence of ouabain yielded a significantly higher percentage of cardiomyocytes. Ouabain was also reported to inhibit Na+/K+-ATPase and followed with altered activity of the functionally coupled sodium-calcium exchanger (NCX-1). In our previous studies, the α1 and 2- isoforms of Na+/K+-ATPase, on which the cardiac predominant ouabain acts, were also increased in differentiated mESCs. Furthermore, among the three major MAPK cascades involved in hypertrophic response pathways, it was found that ouabain rescued the blockage of cardiac differentiation by the ERK1/2 pathway inhibitor, U0126. Interestingly, cardiomyocytes isolated from ouabain-treated mESCs exhibited more mature calcium handling kinetics. The higher amplitudes of caffeine-induced Ca2+ transient suggested a more mature sarcoplasmic recticulum (SR). Ouabain induced cardiac differentiation of mESC and maturation of mESC-CMCs probably via activation of ERK1/2. Further studies are necessary to investigate if ERK1/2 pathway plays a direct role in SR function that governing efficient calcium homeostasis of ESC-CMCs.-
dc.languageengen_US
dc.publisherSpringer-
dc.relation.ispartofStem cells and cancer stem cells. Volume 6, Therapeutic applications in disease and injuryen_US
dc.subjectEmbryonic stem cells.-
dc.titleDifferentiation of embryonic stem cells into cardiomyocytes: role of ouabainen_US
dc.typeBook_Chapteren_US
dc.identifier.emailLee, YK: carol801@hku.hken_US
dc.identifier.emailNg, KM: h9925586@graduate.hku.hken_US
dc.identifier.emailLai, KWH: kwhlai@hku.hken_US
dc.identifier.emailChan, YC: yauchi@graduate.hku.hken_US
dc.identifier.emailLau, VYM: vymlau@hku.hken_US
dc.identifier.emailTse, HF: hftse@hkucc.hku.hken_US
dc.identifier.emailSiu, DCW: cwdsiu@hkucc.hku.hken_US
dc.identifier.authorityNg, KM=rp01670en_US
dc.identifier.authorityChan, YC=rp01502en_US
dc.identifier.authorityTse, HF=rp00428en_US
dc.identifier.doi10.1007/978-94-007-2993-3_7-
dc.identifier.hkuros200849en_US
dc.identifier.volume6-
dc.identifier.spage71-
dc.identifier.epage76-
dc.publisher.placeDordrecht-
dc.customcontrol.immutableyiu 130827-

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