Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells.
Cardiomyocytes generated from embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells are suggested for repopulation of destroyed myocardium. Because contractile properties are crucial for functional regeneration, we compared cardiomyocytes differentiated from ES cells (ESC-CMs) and iPS cells (iPS-CMs). Native myocardium served as control. Murine ESCs or iPS cells were differentiated 11 d in vitro and cocultured 5-7 d with irreversibly injured myocardial tissue slices. Vital embryonic ventricular tissue slices of similar age served for comparison. Force-frequency relationship (FFR), effects of Ca(2+), Ni(2+), nifedipine, ryanodine, beta-adrenergic, and muscarinic modulation were studied during loaded contractions. FFR was negative for ESC-CMs and iPS-CMs. FFR was positive for embryonic tissue and turned negative after treatment with ryanodine. In all groups, force of contraction and relaxation time increased with the concentration of Ca(2+) and decreased with nifedipine. Force was reduced by Ni(2+). Isoproterenol (1 microM) increased the force most pronounced in embryonic tissue (207+/-31%, n=7; ESC-CMs: 123+/-5%, n=4; iPS-CMs: 120+/-4%, n=8). EC(50) values were similar. Contractile properties of iPS-CMs and ESC-CMs were similar, but they were significantly different from ventricular tissue of comparable age. The results indicate immaturity of the sarcoplasmic reticulum and the beta-adrenergic response of iPS-CMs and ESC-CMs.
Xi
Jiaoya
J
Institute for Neurophysiology, University of Cologne, Cologne, Germany.
Khalil
Markus
M
Shishechian
Nava
N
Hannes
Tobias
T
Pfannkuche
Kurt
K
Liang
Huamin
H
Fatima
Azra
A
Haustein
Moritz
M
Suhr
Frank
F
Bloch
Wilhelm
W
Reppel
Michael
M
Sarić
Tomo
T
Wernig
Marius
M
Jänisch
Rudolf
R
Brockmeier
Konrad
K
Hescheler
Jürgen
J
Pillekamp
Frank
F
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology*; D006352:Heart Ventricles / Q000166:cytology*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000166:cytology*; D009543:Nifedipine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D009543:Nifedipine; D002118:Calcium