Why the study?
Altered contractility can cause fatal consequences, so drug discovery would benefit greatly from reliable testing of candidate molecule effects on contractility.
Does exposure to inotropic drugs alter contraction force and beating rate in human cell-based vascularized cardiac tissue constructs measured by a dual-axis piezoelectric force sensor?
Does exposure to inotropic drugs alter contraction force and beating rate in human cell-based vascularized cardiac tissue constructs measured by a dual-axis piezoelectric force sensor?
A novel dual-axis piezoelectric force sensor successfully measured chronotropic and inotropic responses to various drugs in human cell-based vascularized cardiac tissue constructs, offering a potential tool for preclinical cardiotoxicity and efficacy screening.
Should not yet change practice; leaves open whether force variability and hiPSC-CM immaturity limit this platform as a standardized inotropic screen.
Contractility is one of the most crucial functions of the heart because it is directly related to the maintenance of blood perfusion throughout the body. Both increase and decrease in contractility may cause fatal consequences. Therefore, drug discovery would benefit greatly from reliable testing of candidate molecule effects on contractility capacity. In this study, we further developed a dual-axis piezoelectric force sensor together with our human cell-based vascularized cardiac tissue constructs for cardiac contraction force measurements. The capability to detect drug-induced inotropic effects was tested with a set of known positive and negative inotropic compounds of isoprenaline, milrinone, omecamtiv mecarbil, propranolol, or verapamil in different concentrations. Both positive and negative inotropic effects were measurable, showing that our cardiac contraction force measurement system including a piezoelectric cantilever sensor and a human cell-based cardiac tissue constructs has the potential to be used for testing of inotropic drug effects.
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Koivisto et al. (2022) studied this question.
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