Tim Meyer
University Medical Center of Göttingen, Germany
Title: Engineered human myocardium for Safety and Efficacy Screens of Cardioactive Compounds
Biography
Biography: Tim Meyer
Abstract
We employ engineered human myocardium (EHM) as patient-centric model for preclinical safety and efficacy screens, replacing animal research.
Based on the spontaneous and stimulated auxotonic contraction exhibited by EHM we developed a 48 well screening plate for chronic and acute screens of potentially cardio-active compounds. EHM are cast and suspended on fluorescent rubber poles generating a defined restoring force, contractions are recorded at high spatial (20µm) and temporal (20ms) resolution and analyzed in real time using special purpose image recognition hardware. Based on contraction frequency and amplitude we determine, besides others, inotropic, chronotropic, lusotropic and arrhythmogenic responses to treatment.
Our video-optical measurements are sterile and non-perturbing allowing successive measurements over weeks and months to follow tissue maturation and chronic effects. Continuous electrical stimulation may be applied for improved maturation and as a tachycardia model. Poles with increasing stiffness simulate pressure overload. The screening platform is validated against reference compounds, comparison to our classical isometric organ bath measurements and clinical data.