Using engineered tissues to create a small working simulacrum of a beating heart, researchers at GlaxoSmithKline and TARA Biosystems aim to predict how the body’s cardiovascular system responds to potential therapies.
TARA’s 3D “heart-on-a-chip” system was able to accurately replicate human drug responses, according to a study published in the journal Toxicological Sciences—something that’s been difficult to achieve with in vitro testing or animal models.
With cardiac toxicity affecting almost half of new medicine recalls, effective preclinical testing and safety assessments are essential, the two companies said.
To construct the tissues, TARA took induced pluripotent stem cells and cultivated them into cardiomyocytes, the muscle cells of the heart. By directing the cells’ differentiation and conditioning them with electrical fields over a period of weeks, researchers were able to build distinct tissues that mimic the contractions of the atria and ventricles, as well as their drug responses and gene expression. Their work was published earlier this year in Cell.
By measuring how strongly the engineered tissues contract when dosed with different drugs, the companies can get a sense of how potential therapies may affect a healthy human heart’s ability to pump blood to the body. Researchers also saw that the drugs acted along the same molecular pathways seen in human heart tissue.
Additionally, by using stem cells derived from certain patients, the platform could also be used to model different heart diseases, according to TARA.
GSK applied a panel of drugs with known efficacy and toxicity profiles, in order to compare TARA’s platform with other preclinical drug screening methods. These include its responses to blood pressure medications, such as Procardia (nifedipine), Isuprel (isoproterenol) and Digox (digoxin), as well as drugs being studied in heart failure, like dobutamine and omecamtiv.
In January, TARA launched a drug discovery collaboration with Insilico Medicine, focused on cardiovascular disease and cardiac muscle aging. The two aim to combine Insilico’s AI-powered discovery engine with TARA’s tissue models for testing.
Video courtesy of TARA Biosystems.