Human engineered heart tissue as a model system for drug testing
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Human engineered heart tissue as a model system for drug testing. / Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas.
In: ADV DRUG DELIVER REV, Vol. 96, 15.01.2016, p. 214-24.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Human engineered heart tissue as a model system for drug testing
AU - Eder, Alexandra
AU - Vollert, Ingra
AU - Hansen, Arne
AU - Eschenhagen, Thomas
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening.
AB - Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening.
KW - Action Potentials
KW - Animals
KW - Drug Evaluation, Preclinical
KW - Heart
KW - Humans
KW - Induced Pluripotent Stem Cells
KW - Myocardial Contraction
KW - Myocytes, Cardiac
KW - Species Specificity
KW - Tissue Engineering
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Review
U2 - 10.1016/j.addr.2015.05.010
DO - 10.1016/j.addr.2015.05.010
M3 - SCORING: Journal article
C2 - 26026976
VL - 96
SP - 214
EP - 224
JO - ADV DRUG DELIVER REV
JF - ADV DRUG DELIVER REV
SN - 0169-409X
ER -
