Engineered Heart Tissues for Cardiotoxicity Screening

Drugs commonly have pro-arrhythmic effect on the heart that limits their safety margin
Several other drugs have been withdrawn from the market due to lethal arrhythmia
New cancer drugs often interfere with growth factor signaling cascades that are required for tumor expansion, but unfortunately also for the maintenance of normal heart function
Thousands of new compounds are in development and the demand for sensitive and specific experimental systems to detect cardio toxicity is increasing.
Authorities require extensive testing for pro arrhythmic effects of every new licensed drug.
The current panel of tests is of limited predictive value, labor-intensive and expensive. Thus, there is a clear need for improved tests.

Freshly isolated rat neonatal cardiac myocytes (or mouse embryonic stem cells) are mixed with collagen I and growth factors and pipetted in a circular dish with a silicone bottom
The cell-populated hydrogel condenses around a central cylinder in the dish and forms 3D EHT ring around it.
After 12-14 days, the EHT rings are transferred to organ baths to record isometric force of contraction and other readouts

Sample data has been generated using EHTs to test the following:

New Arrays