The gifs above show the newest in an expanding selection of living cells grown in devices to model human organs. This one comes from the University of California, Berkeley, where researchers have grown human heart cells derived from adult stem cells in a one-inch silicone housing. The system is being developed to test how different drugs and compounds would work on the actual organ.
The top gif shows the heart cells beating normally. The gif below it shows the cells after they have been exposed to isoproterenol, a drug used to treat several heart problems including bradycardia, a condition in which the heart rate is too slow. The cells in the lower gif beat significantly faster 30 minutes after coming into contact with the drug.
“Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy,” said bioengineering professor Kevin Healy. This would be a significant improvement over the current model used in the pharmaceutical pipeline since the biology of animal test subjects differs significantly from humans. Such differences lead to inaccurate findings about new drugs’ efficacy and toxicity once used on people.
The system, said postdoctoral researcher Anurag Mathur, is much more than a culture with cells sitting in a nutrient bath. Instead, the team’s heart on a chip includes microfluidic channels on either side of the cell group that mimic blood vessels by diffusing nutrients and experimental drugs into the tissue. “We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs,” said Mathur, who led the study that was published yesterday on the work in the journal Nature Scientific Reports.
Once adult induced pluripotent stem cells are transformed into cardiac cells, they start beating on their own at the normal rate of 55 to 80 beats per minute. Then to test whether the system worked, the researchers exposed the cells, which had been loaded into the chip, to four well-understood pharmaceuticals that either raise or lower heart rate. All caused the cells to behave as they would be expected to if they belonged to an actual patient. While still early, the team is excited by the results of their lab work and conclude in the paper, “We anticipate the widespread adoption of [organ-on-a-chip microphysiological systems] for drug screening and disease modeling.”
Next, the group will investigate whether the modeled heart can be linked to another organ on a chip like one that mimics a human liver to follow experimental drugs as they move through systems.
“Linking heart and liver tissue would allow us to determine whether a drug that initially works fine in the heart might later be metabolized by the liver in a way that would be toxic,” said Healy.
(The “heart-on-a-chip” developed at UC Berkeley houses human heart tissue derived from adult stem cells. The system could one day replace animal models for drug safety screening. Photo courtesy of Anurag Mathur, Healy Lab.
Gifs created from Youtube video courtesy of Anurag Mathur, Healy Lab/UC Berkeley.