Abstract P1131: Modeling Contractile Diseases Using Scalable 3D Engineered Heart Tissues For Drug Discovery

• DOI: 10.1161/res.131.suppl_1.p1131
• Publication Date: 2022-11-14T14:52:03Z
• Authors: Nicholas Geisse; Bonnie Berry; Kevin Gray; Samir Kharoufeh; Shawn M Luttrell; Jesse Macadangdang; Christal Worthen
• Keywords: Cardiotoxicity

Model systems that accurately recapitulate healthy and diseased function in a dish are critical for the development of novel therapeutics. For cardiac diseases, direct assessment contractile output constitutes most reliable metric with which to assess overall tissue function, as other ‘proxy’ measurements poor predictors muscle strength. 3D engineered tissues (EMTs) derived from iPSCs hold great potential modeling function. Here, we have developed platform device utilizes EMTs conjunction label-free magnetic sensing array. The enables facile reproducible fabrication using virtually any cell source is coupled highly parallel measurement This approach stratification phenotypes facilitates compound safety efficacy screening evaluation drug’s effect on output. We will present data drug (BMS-986094) failed clinical trials due unanticipated cardiotoxicity. go show both acute chronic effects doxorubicin EMTs. Contractile force decreased dose dependent-like manner when was applied continuously. Interestingly, single 1uM bolus induced transient could be washed out over time. A repeat bolus, however, irreversibly abolished contraction, suggesting dosing may cardiotoxic muscle. These demonstrate first-and-only commercial high-throughput contraction widespread adoption within field.