BioCentury
ARTICLE | Distillery Techniques

Disease models

January 23, 2019 12:06 AM UTC

A 3-D human tissue model that mimics beating adult myocardium could help assess the effects of heart disease therapies on myocardial contractility. Generation and use of the biomimetic model involves five steps: preparing tissue slices from explants of failing human hearts; attaching one end of the muscle to a steel spring wire with an elastic constant that replicates normal systolic left ventricular wall tension; attaching the other end to a linear drive that is manually adjusted to generate a normal diastolic preload; stimulating tissue with an adjustable current to induce regular contractions; and using signals from magnetic field sensors to measure contractile performance in response to drugs or mechanical stretch for up to 16 weeks. When applied to tissue samples from six patients with a range of heart diseases treated with the generic adrenergic receptor β2 (ADRB2) agonist isoprenaline and exposed to mechanical stretch, contractile performance was comparable to that of fresh, undiseased tissue. In one of the samples, the model accurately measured changes in refractory period induced by treatment with the generic potassium channel Kv11.1 (KCNH2; hERG) inhibitor pentamidine, as confirmed by intracellular potential recordings in the sample. Next steps could include assessing other heart disease therapies in the model.

Isoprenaline is marketed to treat bradycardia and heart block...