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Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation

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Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. / Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas.

In: J MOL CELL CARDIOL, Vol. 74C, 19.05.2014, p. 151-161.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hirt, MN, Boeddinghaus, J, Mitchell, A, Schaaf, S, Börnchen, C, Müller, C, Schulz, H, Hubner, N, Stenzig, J, Stoehr, A, Neuber, C, Eder, A, Luther, PK, Hansen, A & Eschenhagen, T 2014, 'Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation', J MOL CELL CARDIOL, vol. 74C, pp. 151-161. https://doi.org/10.1016/j.yjmcc.2014.05.009

APA

Hirt, M. N., Boeddinghaus, J., Mitchell, A., Schaaf, S., Börnchen, C., Müller, C., Schulz, H., Hubner, N., Stenzig, J., Stoehr, A., Neuber, C., Eder, A., Luther, P. K., Hansen, A., & Eschenhagen, T. (2014). Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J MOL CELL CARDIOL, 74C, 151-161. https://doi.org/10.1016/j.yjmcc.2014.05.009

Vancouver

Hirt MN, Boeddinghaus J, Mitchell A, Schaaf S, Börnchen C, Müller C et al. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J MOL CELL CARDIOL. 2014 May 19;74C:151-161. https://doi.org/10.1016/j.yjmcc.2014.05.009

Bibtex

@article{3ddcdbe6812f449d9c0c840bef4d9894,
title = "Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation",
abstract = "Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.",
author = "Hirt, {Marc N} and Jasper Boeddinghaus and Alice Mitchell and Sebastian Schaaf and Christian B{\"o}rnchen and Christian M{\"u}ller and Herbert Schulz and Norbert Hubner and Justus Stenzig and Andrea Stoehr and Christiane Neuber and Alexandra Eder and Luther, {Pradeep K} and Arne Hansen and Thomas Eschenhagen",
note = "Copyright {\textcopyright} 2014. Published by Elsevier Ltd.",
year = "2014",
month = may,
day = "19",
doi = "10.1016/j.yjmcc.2014.05.009",
language = "English",
volume = "74C",
pages = "151--161",
journal = "J MOL CELL CARDIOL",
issn = "0022-2828",
publisher = "Academic Press Inc.",

}

RIS

TY - JOUR

T1 - Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation

AU - Hirt, Marc N

AU - Boeddinghaus, Jasper

AU - Mitchell, Alice

AU - Schaaf, Sebastian

AU - Börnchen, Christian

AU - Müller, Christian

AU - Schulz, Herbert

AU - Hubner, Norbert

AU - Stenzig, Justus

AU - Stoehr, Andrea

AU - Neuber, Christiane

AU - Eder, Alexandra

AU - Luther, Pradeep K

AU - Hansen, Arne

AU - Eschenhagen, Thomas

N1 - Copyright © 2014. Published by Elsevier Ltd.

PY - 2014/5/19

Y1 - 2014/5/19

N2 - Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

AB - Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

U2 - 10.1016/j.yjmcc.2014.05.009

DO - 10.1016/j.yjmcc.2014.05.009

M3 - SCORING: Journal article

C2 - 24852842

VL - 74C

SP - 151

EP - 161

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

ER -