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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

TitleRegulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel
Authors
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/
Citation
American Journal Of Physiology - Cell Physiology, 2012, v. 303 n. 2, p. C115-C125 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/163516
ISSN
2014 Impact Factor: 3.780
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Jen_US
dc.contributor.authorChan, YCen_US
dc.contributor.authorHo, JCYen_US
dc.contributor.authorSiu, CWen_US
dc.contributor.authorLian, Qen_US
dc.contributor.authorTse, HFen_US
dc.date.accessioned2012-09-05T05:32:57Z-
dc.date.available2012-09-05T05:32:57Z-
dc.date.issued2012en_US
dc.identifier.citationAmerican Journal Of Physiology - Cell Physiology, 2012, v. 303 n. 2, p. C115-C125en_US
dc.identifier.issn0363-6143en_US
dc.identifier.urihttp://hdl.handle.net/10722/163516-
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.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpcell.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Cell Physiologyen_US
dc.subject3-(4,5-Dimethyl-Thiazol-2-Yl)-2,5-Dephenyltetrazolium Bromideen_US
dc.subjectBromodeoxyuridineen_US
dc.subjectPatch Clampen_US
dc.titleRegulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channelen_US
dc.typeArticleen_US
dc.identifier.emailChan, YC:yauchi@graduate.hku.hken_US
dc.identifier.emailLian, Q:qzlian@hkucc.hku.hken_US
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_US
dc.identifier.authorityChan, YC=rp01502en_US
dc.identifier.authorityLian, Q=rp00267en_US
dc.identifier.authorityTse, HF=rp00428en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1152/ajpcell.00326.2011en_US
dc.identifier.pmid22357737-
dc.identifier.scopuseid_2-s2.0-84863901864en_US
dc.identifier.hkuros185840-
dc.identifier.hkuros203415-
dc.identifier.hkuros205604-
dc.identifier.hkuros205612-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84863901864&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume303en_US
dc.identifier.issue2en_US
dc.identifier.spageC115en_US
dc.identifier.epageC125en_US
dc.identifier.isiWOS:000306423100002-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhang, J=55316200700en_US
dc.identifier.scopusauthoridChan, YC=7403676116en_US
dc.identifier.scopusauthoridHo, JCY=7402650173en_US
dc.identifier.scopusauthoridSiu, CW=55164929800en_US
dc.identifier.scopusauthoridLian, Q=7003399023en_US
dc.identifier.scopusauthoridTse, HF=7006070805en_US

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