Long-term ex-vivo culture of human HCM myocardial slices retains certain disease-specific signatures like myosin SRX-DRX ratio, but requires further optimization to prevent changes in force and metabolism.
To better understand pathomechanisms and drug responses in hypertrophic cardiomyopathy (HCM), long-term, reproducible human models for intact cardiac muscle are needed. To this end, we used the MyoDish tissue culture system for a 28-day culture of 73 living myocardial slices (LMSs) derived from myectomy samples of 14 HCM-patients. We defined the model's applicability in HCM by measuring contractility, myosin super relaxed to disordered relaxed state (SRX-DRX) ratios, mitochondrial function, and metabolic/proteomic profiles in LMS at days (D) 0, 14, and 28. Prominent changes in force, mitochondrial function, protein expression, and metabolism appeared in D14 and D28 slices compared to D0 (non-cultured) slices. Notably, the myosin SRX-DRX ratio and microtubule signatures were retained between D0 and D28, and contractility parameters were unchanged between D8 and D14. Our study indicates that drug interventions targeting these pathways are feasible, though culture conditions require further optimization to fully preserve an HCM-patient-specific profile.
Nassar et al. (Wed,) studied this question.