July 10, 2018Open Access
Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems
View Full Paper
Ask AI
Bookmark
Share
Key result
A computational framework successfully inverted optically obtained voltage and calcium waveforms from immature human stem cell-derived cardiomyocytes to identify drug-induced ion channel blockages and predict their effects in mature cells.
Population
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in microphysiological systems (MPS)
Comparison
Application of verapamil and cisapride combined… vs Control conditions
Design
Preclinical
Follow-up
5 minutes of exposure per dose
Authors
Discussion
Loading...
Member takes
Implication
Framework enables drug action identification from immature hiPSC-CMs; hypothesis-generating for cardiac safety screening.
Structured PICO
P
Population
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in microphysiological systems (MPS)
I
Intervention
Application of verapamil (100 nM) and cisapride (10 nM) combined with computational inversion of optical voltage and calcium waveforms
C
Comparator
Control conditions (baseline before drug application)
O
Outcome
Identification of drug-induced ion channel blockage (ICaL and IKr) and prediction of action potential changes in mature cellssurrogate
A novel computational framework can invert optical voltage and calcium measurements from immature hiPSC-CMs to accurately predict drug-induced ion channel blockages and action potential changes in mature cardiomyocytes.
Limitations
- Variability in hiPSC-CMs remains a challenge for batch to batch consistency.
- Voltage waveform cannot currently be imaged at the time resolution needed to obtain accurate measurements of the upstroke.
- Signal to noise ratio prevents adequate resolution of the plateau phase and notch, preventing inversion of the Ito current.
- Cost function using voltage alone is largely insensitive to changes in Ito and IKs
- Upstroke velocity of the action potential could not be added to the voltage cost function due to insufficient measurement accuracy
Cite This Study
Tveito et al. (2018) studied Cardiotoxicity. Computational maturation framework was evaluated on Identification of drug ion channel blockage and prediction of mature cell action potential. A computational framework successfully inverted optically obtained voltage and calcium waveforms from immature human stem cell-derived cardiomyocytes to identify drug-induced ion channel blockages and predict their effects in mature cells.
View Full Paper
Ask AI
Bookmark
Share