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5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells

Cell Research 2006年第12期16卷 949-960页

作者： Bartosz Balana cecilia nicolett Ihor Zahanich Eva M Graf Torsten Christ Sabine Boxberger Department of Pharmacology and Toxicology Medical Clinic I Medical FacultyDresden University of TechnologyFetscherstr.74D-01307 DresdenGermany

Previously,mouse bone marrow-derived stem cells（MSC）treated with the unspecific DNA methyltransferase inhibi-tor 5-azacytidine were reported to differentiate into *** aim of the present study was to investigate theefficiency of a similar differentiation strategy in human mononuclear cells obtained from healthy bone marrow *** 1-3 passages,cultures were exposed for 24 h to 5-azacytidine（3μM）followed by 6 weeks of further *** treatment did not induce expression of myogenic marker MyoD or cardiac markers Nkx2.5 and GATA-4 and didnot yield beating cells during *** patch clamp experiments,approximately 10-15% of treated and untreatedcells exhibited L-type Ca2+ *** all cells showed outwardly rectifying K+currents of rapid or slow *** current amplitude at +60 mV doubled after 6 weeks of treatment compared with time-matched *** capacitance of treated cells was significantly larger than in controls 2 weeks after treatment and remained highafter 6 *** levels ofmRNAs for the K+channels Kv1.1,Kv1.5,Kv2.1,Kv4.3 and KCNMA1 and for theCa2+ channel Cav1.2 were not affected by *** with potassium channel blockers tetraethylammoniumand clofilium at concentrations shown previously to inhibit rapid or slowly activating K+currents of hMSC inhibitedproliferation of these *** results suggest that despite the absence of differentiation of hMSC into cardiomyocytes,treatment with 5-azacytidine caused profound changes in current density.

关键词： human mesenchymal stem cells 5-azacytidine cardiac differentiation outward K~+ currents

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