March 16, 2015

Due to inefficiencies in the drug discovery and development process, and because animal models do not sufficiently represent human biology, researchers at the University of California, Berkeley have developed a human-relevant in vitro model to better predict drug-induced toxicity of the heart (cardiotoxicity). The need to develop better, more predictive in vitro screens is critical, as cardiotoxicity is one of the main reasons that drugs are withdrawn from the market. This is because animal models, in many cases, do not accurately predict human cardiotoxicity due to a number of biological differences.

To address this deficiency, researchers have developed a three-dimensional heart microphysiological system derived from human-induced pluripotent stem cells. According to lead author Anurag Mathur, “This system is not a simple cell culture where tissue is being bathed in a static bath of liquid.” And that is the truth! In this sophisticated model, the cardiac microtissue has physiologically-relevant tissue structure, and the heart cells even beat at the normal physiological rate of 55-80 beats per minute. The model also contains mini-channels to mimic blood vessels that transport nutrients and drugs to the tissue.

And when researchers used beat rate as an endpoint to examine the effect of well-characterized cardiovascular drugs on this model, the results showed good agreement with clinical observations. For instance, a drug that is used to treat slow heart rate increased the beat rate of the heart-on-a-chip model.

This model can be easily scaled up and can even be modified to examine different human genetic diseases by using cells derived from different patients. Models of this type could also significantly reduce the time and cost of bringing new drugs to market.

While in the short term, the researchers envision this model as a complement to animal models, they also believe the potential exists for the heart-on-a-chip to one day replace animal studies, “which often are expensive, unethical, and do not predict the drug’s actual effect.”

What do you think of this heart-on-a-chip model? Send your questions and comments to sciencecorner@navs.org. I look forward to hearing from you.

–Dr. Pam Osenkowski, Director of Science Programs

When UC 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.

For more information see: University of California Berkeley News Center

For the primary article discussing this research see: Scientific Reports