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Article: Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel
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TitleRegulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel
 
AuthorsZhang, J2
Chan, YC2
Ho, JCY2 1
Siu, CW2 1
Lian, Q2 1
Tse, HF2 1
 
Keywords3-(4,5-Dimethyl-Thiazol-2-Yl)-2,5-Dephenyltetrazolium Bromide
Bromodeoxyuridine
Patch Clamp
 
Issue Date2012
 
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
 
CitationAmerican Journal Of Physiology - Cell Physiology, 2012, v. 303 n. 2, p. C115-C125 [How to Cite?]
DOI: http://dx.doi.org/10.1152/ajpcell.00326.2011
 
AbstractThe successful generation of a high yield of mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (iPSCs) may represent an unlimited cell source with superior therapeutic benefits for tissue regeneration to bone marrow (BM)-derived MSCs. We investigated whether the differential expression of ion channels in iPSC-MSCs was responsible for their higher proliferation capacity than BM-MSCs. The expression of ion channels for K +, Na +, Ca 2+, and Cl - was examined by RT-PCR. The electrophysiological properties of iPSC-MSCs and BM-MSCs were then compared by patch-clamp experiments to verify their functional roles. Significant mRNA expression of ion channel genes including KCa1.1, KCa3.1, KCNH1, Kir2.1, SCN9A, CACNA1C, and Clcn3 was observed in both human iPSC-MSCs and BM-MSCs, whereas Kir2.2 and Kir2.3 were only detected in human iPSC-MSCs. Five types of currents [big-conductance Ca 2+-activated K + current (BK Ca), delayed rectifier K + current (IK DR), inwardly rectifying K + current (I Kir), Ca 2+-activated K + current (IK Ca), and chloride current (I Cl)] were found in iPSC-MSCs (83%, 47%, 11%, 5%, and 4%, respectively) but only four of them (BK Ca, IK DR, I Kir, and IK Ca) were identified in BM-MSCs (76%, 25%, 22%, and 11%, respectively). Cell proliferation was examined with MTT or bromodeoxyuridine assay, and doubling times were 2.66 and 3.72 days for iPSC-MSCs and BM-MSCs, respectively, showing a 1.4-fold discrepancy. Blockade of IK DR with short hairpin RNA or human ether-à-go-go 1 (hEAG1) channel blockers, 4-AP and astemizole, significantly reduced the rate of proliferation of human iPSC-MSCs. These treatments also decreased the rate of proliferation of human BM-MSCs albeit to a lesser extent. These findings demonstrate that the hEAG1 channel plays a crucial role in controlling the proliferation rate of human iPSC-MSCs and to a lesser extent in BM-MSCs. © 2012 the American Physiological Society.
 
ISSN0363-6143
2013 Impact Factor: 3.674
 
DOIhttp://dx.doi.org/10.1152/ajpcell.00326.2011
 
ISI Accession Number IDWOS:000306423100002
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, J
 
dc.contributor.authorChan, YC
 
dc.contributor.authorHo, JCY
 
dc.contributor.authorSiu, CW
 
dc.contributor.authorLian, Q
 
dc.contributor.authorTse, HF
 
dc.date.accessioned2012-09-05T05:32:57Z
 
dc.date.available2012-09-05T05:32:57Z
 
dc.date.issued2012
 
dc.description.abstractThe successful generation of a high yield of mesenchymal stem cells (MSCs) from human induced pluripotent stem cells (iPSCs) may represent an unlimited cell source with superior therapeutic benefits for tissue regeneration to bone marrow (BM)-derived MSCs. We investigated whether the differential expression of ion channels in iPSC-MSCs was responsible for their higher proliferation capacity than BM-MSCs. The expression of ion channels for K +, Na +, Ca 2+, and Cl - was examined by RT-PCR. The electrophysiological properties of iPSC-MSCs and BM-MSCs were then compared by patch-clamp experiments to verify their functional roles. Significant mRNA expression of ion channel genes including KCa1.1, KCa3.1, KCNH1, Kir2.1, SCN9A, CACNA1C, and Clcn3 was observed in both human iPSC-MSCs and BM-MSCs, whereas Kir2.2 and Kir2.3 were only detected in human iPSC-MSCs. Five types of currents [big-conductance Ca 2+-activated K + current (BK Ca), delayed rectifier K + current (IK DR), inwardly rectifying K + current (I Kir), Ca 2+-activated K + current (IK Ca), and chloride current (I Cl)] were found in iPSC-MSCs (83%, 47%, 11%, 5%, and 4%, respectively) but only four of them (BK Ca, IK DR, I Kir, and IK Ca) were identified in BM-MSCs (76%, 25%, 22%, and 11%, respectively). Cell proliferation was examined with MTT or bromodeoxyuridine assay, and doubling times were 2.66 and 3.72 days for iPSC-MSCs and BM-MSCs, respectively, showing a 1.4-fold discrepancy. Blockade of IK DR with short hairpin RNA or human ether-à-go-go 1 (hEAG1) channel blockers, 4-AP and astemizole, significantly reduced the rate of proliferation of human iPSC-MSCs. These treatments also decreased the rate of proliferation of human BM-MSCs albeit to a lesser extent. These findings demonstrate that the hEAG1 channel plays a crucial role in controlling the proliferation rate of human iPSC-MSCs and to a lesser extent in BM-MSCs. © 2012 the American Physiological Society.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 2012, v. 303 n. 2, p. C115-C125 [How to Cite?]
DOI: http://dx.doi.org/10.1152/ajpcell.00326.2011
 
dc.identifier.doihttp://dx.doi.org/10.1152/ajpcell.00326.2011
 
dc.identifier.epageC125
 
dc.identifier.hkuros185840
 
dc.identifier.hkuros203415
 
dc.identifier.hkuros205604
 
dc.identifier.hkuros205612
 
dc.identifier.isiWOS:000306423100002
 
dc.identifier.issn0363-6143
2013 Impact Factor: 3.674
 
dc.identifier.issue2
 
dc.identifier.pmid22357737
 
dc.identifier.scopuseid_2-s2.0-84863901864
 
dc.identifier.spageC115
 
dc.identifier.urihttp://hdl.handle.net/10722/163516
 
dc.identifier.volume303
 
dc.languageeng
 
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiology
 
dc.relation.referencesReferences in Scopus
 
dc.subject3-(4,5-Dimethyl-Thiazol-2-Yl)-2,5-Dephenyltetrazolium Bromide
 
dc.subjectBromodeoxyuridine
 
dc.subjectPatch Clamp
 
dc.titleRegulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong