Oncology Drugs: “Human Heart” on Chip for Toxicity Testing

A “human heart” on a silicone chip to assess the cardiac toxicity effects caused by oncology drugs. The discovery by American researchers.

A cardiovascular organ-chip as an experimental platform for studying the cardiotoxic effects of cancer drugs. An instrument made from pluripotent stem cells differentiated into cardiac and vascular cells then mounted on a silicon material. This is the result of studies by researchers at Cedars-Sinai Medical Center in Los Angeles and published in the Lab on a Chip journal of the Royal Society of Chemistry.

From in vitro models to organ-chips

Cardiovascular toxicity causes adverse reactions to drugs and can lead to the removal of drugs from the pharmaceutical market. Cancer therapies can induce potentially lethal cardiovascular side effects such as arrhythmias, necrosis of muscle cells, or vascular dysfunction. New technologies have allowed the identification of cardiotoxic compounds in the early stages of drug development.

Cardiomyocytes (CM) and vascular endothelial cells (EC) derived from human induced pluripotent stem cells (hiPSC) can be used to detect drug-induced alterations in the function and survival of cardiovascular cells. However, most existing hiPSC models for cardiovascular toxicity use immature two-dimensional cells grown in static culture. Improved in vitro models to investigate cardiotoxicity would use mature hiPSC cells resembling adults in an integrated system where toxic drugs and protective agents can flow between hiPSC-EC representing the systemic vascular system and hiPSC-CM representing cardiac muscle (myocardium). Such models would be useful for testing the multi-linear cardiotoxicities of chemotherapeutic drugs such as VEGFR2/PDGFR tyrosine kinase inhibitors (VPTKI).

The "heart"-chip: differentiated pluripotent stem cells and silicone support

In this case, the new cardiovascular organ-chip, multi-linear and fully integrated, is capable of reproducing about 60 beats per minute and was made from human induced pluripotent stem cells, which were differentiated into cardiomyocytes and endothelial cells. Then they were deposited on a flexible silicone material called polydimethylsiloxane. The main peculiarity of the chip is given by the presence of two parallel channels that allow cardiomyocytes and endothelial cells to be separated as in the human body while remaining close enough to interact.

By simulating blood flow and mechanical movements of the heart in response to drug administration, this platform allows predicting their toxicity, which can cause arrhythmias or even death of cardiac muscle cells. Effects can also be monitored in the long term, as the heart-on-chip remains functional for several weeks.

We demonstrate the usefulness of this cardiovascular organ-chip as a predictive platform for evaluating the multi-linear toxicity of VPTKI. This study could lead to the development of new methods for the assessment and prevention of cancer therapy-induced cardiotoxicity“.