A polystyrene-film-based device for engineered cardiac tissues enables accurate analysis of drug responses on contractile properties

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Abstract
Engineered heart tissues (EHTs) using human induced pluripotent stem cells provide a valuable in vitro platform for assessing pharmacological and toxicological effects on cardiac functions. EHT devices offer a feasible approach to readily evaluate drug responses on contractile properties, including contractile force and relaxation, by measuring the moving distance of pillars attached to EHTs. However, the absorption of small molecule compounds by polydimethylsiloxane (PDMS), the material commonly used to construct EHT devices, hinders the accurate evaluation of the pharmacodynamic properties of drug candidates on contractility. Here, we developed a low-absorption EHT device using polystyrene (PS) to address this issue. Moreover, we generated an original Python-based analysis program to avoid analytical bias when tracking pillar positions and analyzing the contractile waveform drawn from EHT movements. This analytical platform enables the detection of increased contractile force during EHT maturation and the negative inotropic effects of diltiazem and blebbistatin on EHT contractile functions. Moreover, EHTs with PS-based devices suppressed the absorption of a cardiotoxic drug, doxorubicin, thus allowing the detection of cardiotoxic effects even at low concentrations compared to EHTs grown on PDMS-based devices. Together, our EHT system represents a useful in vitro platform for accurate evaluations of drug responses by the human heart.
Funding Information
  • Kyoto University Foundation
  • Fondation Leducq (18CVD05)
  • Japan Agency for Medical Research and Development (JP20bm0104001, JP21bm0804022, JP24mk0121280, JP22mk0101241, JP23bm1323001, JP23bm1423011, JP24bm1123054)
  • Japan Society for the Promotion of Science (20K16218, 24K19055)
  • Takeda Pharmaceutical Company
  • Program for Creating STart-ups from Advanced Research and Technology (JPMJSF2323)

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