Substantial variation in the cardiac differentiation of human embryonic stem cell lines derived and propagated under the same conditions--a comparison of multiple cell lines.
OBJECTIVE
The differentiation efficiencies of human embryonic stem cell (hESC) lines differ from each other. To assess this in more detail we studied the cardiac differentiation of eight hESC lines derived in the same laboratory.


RESULTS
Substantial variation in growth and in the ability to form beating areas was seen between the different hESC lines; line HS346 gave the best efficiency (9.4%), while HS293 did not differentiate into beating colonies at all. Nine germ layer and differentiation markers were quantified during early differentiation in four hESC lines. The expression levels of Brachyury T, MESP1 and NKX2.5 were highest in the most efficient cardiac line (HS346). A systematic characterization of the beating cells revealed proper cardiac marker expression, electrophysiological activity, and pharmacological response.


CONCLUSIONS
The hESC lines derived in the same laboratory varied considerably in their potential to differentiate into beating cardiomyocytes. None of the expression markers could clearly predict cardiac differentiation potential, although the expression of early cardiomyogenic genes was upregulated in the best cardiac line. The proper cardiomyocyte characteristics and pharmacological response indicate that these cells could be used as a model for human cardiomyocytes in pharmacological and toxicological analyses when investigating new heart medications or cardiac side-effects.
Pekkanen-Mattila
Mari
M
REGEA, Institute for Regenerative Medicine, University of Tampere and Tampere University Hospital, Biokatu 12, Tampere, Finland.
Kerkelä
Erja
E
Tanskanen
Jarno M A
JM
Pietilä
Mika
M
Pelto-Huikko
Markku
M
Hyttinen
Jari
J
Skottman
Heli
H
Suuronen
Riitta
R
Aalto-Setälä
Katriina
K
D015415:Biomarkers / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D024722:Cardiac Myosins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D022062:Electrophysiologic Techniques, Cardiac; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008564:Membrane Potentials / Q000187:drug effects; D016253:Microscopy, Immunoelectron; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology
D015415:Biomarkers; D002121:Calcium Channel Blockers; D012313:RNA; D014700:Verapamil; D024722:Cardiac Myosins