US researchers are investigating how heart cells stored on a silicon chip can help screen drugs for human use.
The ‘heart-on-chip’ is essentially a load of pulsating cardiac muscle cells, placed on a silicon device that holds it all in place, modelling human heart tissue.
Then, by introducing medication to the cells, researchers can better establish how humans may respond to drugs.
At the moment, research into drug use is done on animals and, given the differences between humans and the animals tested, it’s far from fool proof. A good example of this is the ion channels through which heart cells conduct its electrical currents, which can vary in both number and type between species.
“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 Kevin Healy, the researcher leading the team at University of California.
“Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy,” said Healy.
Costs a pretty penny
At the moment, the cost of developing a drug fit for human use is US$5bn, according to Healy, with two-thirds of that price coming from upfront costs in the research and development phase.
Bioengineering something like this could reduce those costs significantly, perhaps even speeding up the process, too.
The construction of the chip is incredibly clever, with the researchers ensuring its 3D make-up is comparable to the geometry of connective tissue fibre in the heart.
Wafers like the one shown here are used to create ‘organ-on-a-chip’ devices to model human tissue. Photo by Anurag Mathur, Healy Lab
“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,” said UC Berkeley’s Sarah Yang. “The system’s confined geometry helps align the cells in multiple layers and in a single direction.”
Adding cells to the chip. Photo by Anurag Mathur, Healy Lab
In less than a day the cells, which were derived from stem cells that can become different types of tissue, started beating.
“This system is not a simple cell culture where tissue is being bathed in a static bath of liquid,” said study lead author Anurag Mathur.
“We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs.”
The video shows cardiac muscle cells before and after exposure to isoproterenol, a drug used to treat certain heart ailments, including bradycardia (slow heart rate). It’s clear that the cells beat faster after 30 minutes of exposure to isoproterenol
The researchers claim their heart-on-a-chip could be adapted to model human genetic diseases or to screen for an individual’s reaction to drugs. They’re also looking at branching out into other multi-organ investigations, whereby a plate could potentially feature hundreds of microphysiological cell culture systems.
“Linking heart and liver tissue would allow us to determine whether a drug that initially works fine in the heart might later be metabolised by the liver in a way that would be toxic,” said Healy.
The engineered heart tissue remained viable and functional over multiple weeks. Given that time, it could be used to test various drugs, Healy said.
The full report has been published in the journal Scientific Reports.
Heart made of chips via Shutterstock