VIDEO:Shown is human heart tissue, derived from adult stem cells, before and after exposure to isoproterenol, a drug used to treat bradycardia (slow heart rate) and other heart problems. The... view more
Credit: Video by Dr. Anurag Mathur/Healy Lab
Berkeley -- When University of California, Berkeley, bioengineers say they are holding their hearts in the palms of their hands, they are not talking about emotional vulnerability.
Instead, the research team led by bioengineering professor Kevin Healy is presenting a network of pulsating cardiac muscle cells housed in an inch-long silicone device that effectively models human heart tissue, and they have demonstrated the viability of this system as a drug-screening tool by testing it with cardiovascular medications.
This organ-on-a-chip, reported in a study to be published Monday, March 9, in the journal Scientific Reports, represents a major step forward in the development of accurate, faster methods of testing for drug toxicity. The project is funded through the Tissue Chip for Drug Screening Initiative, an interagency collaboration launched by the National Institutes of Health to develop 3-D 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 Healy.
The study authors noted a high failure rate associated with the use of nonhuman animal models to predict human reactions to new drugs. Much of this is due to fundamental differences in biology between species, the researchers explained. For instance, the ion channels through which heart cells conduct electrical currents can vary in both number and type between humans and other animals.
"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," said Healy. "It takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."
The heart cells were derived from human-induced pluripotent stem cells, the adult stem cells that can be coaxed to become many different types of tissue.
The researchers designed their cardiac microphysiological system, or heart-on-a-chip, so that its 3-D structure would be comparable to the geometry and spacing of connective tissue fiber in a human heart. They added the differentiated human heart cells into the loading area, a process that Healy likened to passengers boarding a subway train at rush hour. The system's confined geometry helps align the cells in multiple layers and in a single direction.
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Bioengineers put human hearts on a chip to aid drug screening
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