Prescription drugs have enabled millions of Americans with chronic medical conditions to live longer and more fulfilling lives, but many promising new drugs never make it to the human trials stage due to the potential for cardiac toxicity.
A platform called iCHIP (in-vitro Chip-based Human In-vestigational Platform) models a human heart on an engineered chip and measures the effects of drug exposure on functions of heart tissue using microelec-trodes. Using the “heart-on-a-chip,” researchers could decrease the time needed for new drug trials, ensure potentially lifesaving drugs are safe and effective, and reduce the need for human and animal testing.
iCHIP successfully recorded both electrical signals and cellular beating from normal human heart cells grown on a multi-electrode array. The platform allows measurement of the two heart functions — contraction and electrophysiology — for the first time. The ability to record those two functions would be useful to pharmaceutical companies because it could alert drug manufacturers to cardiac problems caused by a drug early in the process before reaching the clinical trial stage. Cardiotoxicity is a frequent side effect of many new drugs and often contributes to their ultimate failure. Other frequently prescribed drugs, such as chemotherapy agents, also are known to be cardiotoxic. Research using the heart chip could provide experimental information about how the drugs work so that new compounds can be designed to avoid these pitfalls.
The heart-on-a-chip involves the use of human cardiac cells cultured for up to nine days on the engineered chip. The cells naturally and spontaneously grow into a two-dimensional heart tissue that contracts or starts to “beat” after two days in culture. The tissue was exposed to norepinephrine, a stimulant drug used to treat low blood pressure and heart failure, and both the electrical signal and the beating increased in the cells, similar to what would happen in the body.
The change in heart rate was measured using the electrodes in the micro-electrode array. The platform could accurately and non-invasively measure heart tissue growth, electrophysiology, and heartbeat simultaneously and in real time. A chemical used to validate the platform decouples the electrical signal from the cell beating. When the cells were exposed to this compound, the electrical signals continued normally, but the cells stopped contracting. Different cell seeding densities were tested to find one that would stay alive long enough, and could measurably contract and respond similarly to what would be expected in humans. The team tested four different modifications of the electrode array before settling on the right one.