Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Drug discovery and development have long been hampered by high failure rates attributed to the reliance on non-human animal models employed during safety and efficacy testing. A fundamental problem in this inefficient process is that non-human animal models cannot adequately represent human biology.

To circumvent the physiological differences inherent in animal model systems, investigators at the University of California, Berkeley (USA) developed a human tissue-based model system using heart cells derived from selectively manipulated human pluripotent stem cells. The cells were induced to grow in a silicon chip device that contained a three-dimensional culture scaffold that was comparable to the geometry and spacing of connective tissue fiber in a human heart. Heart cells were loaded into the chip in multiple layers aligned in a single direction. Microfluidic channels on either side of the growth area served as models for blood vessels, mimicking the exchange by diffusion of nutrients and drugs with human tissue.

Results published in the March 9, 2015, edition of the journal Scientific Reports revealed that within 24 hours after the heart cells were loaded onto the chip, they began beating on their own at a normal physiological rate of 55 to 80 beats per minute. The culture system was able to keep human induced pluripotent stem cell derived cardiac tissue viable and functional over a period of several weeks.

The system was tested by monitoring the reaction of the heart cells to four different cardiovascular drugs: isoproterenol, E-4031, verapamil, and metoprolol. Changes in the heart tissue’s beat rate were monitored to gauge the response to the compounds. The experiment was considered to be a success when—after half an hour of exposure to isoproterenol, a drug used to treat bradycardia—the heart tissue beat rate increased from 55 to 124 beats per minute.

The "heart-on-a-chip" project was sponsored in part by the [US] National Institutes of Health's Tissue Chip for Drug Screening Initiative, an interagency collaboration for the development of three-dimensional human tissue chips that model the structure and function of human organs.

“Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy,” said senior author Dr. Kevin E. Healy, professor of bioengineering at the University of California, Berkeley. “Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market.”

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