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Heart-on-Chip Device Built to Screen Drugs

Heart-on-a-chip device

Heart-on-a-chip device (Anurag Mathur, Healy Lab, Univ. of California-Berkeley)

9 March 2015. A bioengineering team at University of California in Berkeley developed a device with cardiac tissue derived from stem cells that can test drug candidates for potentially toxic effects. Researchers from the lab of engineering professor Kevin Healy published their findings today in the journal Scientific Reports.

Healy and colleagues created this device as part of the Tissue Chip for Drug Screening project, an initiative of National Institutes of Health, Food and Drug Administration, and Defense Advanced Research Projects Agency or Darpa. That initiative aims to come up with alternatives to preclinical toxicity tests using animals, because of their high error rates, before drug candidates reach the stage of human clinical trials.

With the high costs and long durations needed to develop drugs, say the authors, fast and inexpensive methods are needed to find candidates that will work and those that won’t. Screening is particularly needed for drugs that may cause adverse effects in the heart, which account for one-third of drug withdrawals based on safety factors.

The researchers designed the device with a three-dimensional structure comparable to connective tissue in the heart. Heart cells arrayed on the device were derived from human-induced pluripotent stem cells, adult stem cells that can transform into various types of tissue cells. The heart cells then were fed through a funnel-shaped receptacle and distributed on a silicone chip about 1 inch long. The chip also has tiny channels that emulate blood vessels, and their functions in the diffusion of drugs and nutrients in human tissue.

In about 24 hours after seeding the chip, heart tissue cells on the device began beating at 55 to 80 beats per minute, a rate similar to a human heart. The authors report being able to keep the heart tissue cells beating 2 to 3 weeks after seeding the chip.

To test the concept, the researchers exposed the generated heart tissue to 4 heart drugs in concentrations comparable to recommended human dosages:

Isoproteronol, a treatment for slow heart rate

E-4031, a potassium channel blocker for treating heart rhythm problems

Verapamil, a calcium channel blocker to treat high blood pressure and control chest pain

Metoprolol, also a treatment for high blood pressure and chest pain, as well as to improve survival after a heart attack

The team reports the four drugs affect heart beat rates on the device as expected, if given to patients. Isoproterenol, for example, causes increases in heart rate that vary depending on the dosage, while verapamil has the opposite effects, causing decreases in beat rate, also depending on the dosage.

The researchers envision adapting the chip to test for human genetic diseases or screen drugs for an individual’s reactions to drugs, not just for populations overall. Chips for screening toxicity in the heart could also be combined on a single wafer with chips emulating other organs, like the liver, to test for a broader range toxic effects. “Ultimately,” says Healy in a university statement, “these chips could replace the use of animals to screen drugs for safety and efficacy.”

The following brief (22-second) video demonstrates the device with beating heart tissue, as well as the effects of drug exposure.

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