Heart slice system reveals drug cardiotoxicity

A new heart slice culture system is proving its worth in spotting drug-related heart risks, offering a glimpse into how anti-cancer drugs affect human tissue. Developed by researchers like Jessica M Miller and Tamer M A Mohamed, this method keeps 300 μm slices of human and pig hearts alive and ticking for up to six days. In a study published in Toxicology and Applied Pharmacology, the team tested three drugs—doxorubicin, trastuzumab, and sunitinib—known for their heart-damaging potential, and the results, released in 2020, are turning heads.

The setup is straightforward but powerful. After 48 hours of exposure to these drugs at doses from 0.1-1 μM, the heart slices showed clear signs of trouble—shrinking viability, crumbling cardiomyocyte structure, and faltering function. Doxorubicin, a chemotherapy staple, triggered oxidative stress and silenced key cardiac genes, mirroring its real-world toll. Trastuzumab, used for breast cancer, weakened muscle contraction genes, while sunitinib, a kidney cancer fighter, choked off angiogenesis-related genes—each drug’s fingerprint laid bare in the tissue’s response.

What sets this apart from lab-grown stem cell models? The slices nailed sunitinib’s toxicity at clinically relevant levels, where hiPS-derived cardiomyocytes sometimes miss the mark. It’s a human touch—real heart tissue, not just cells in a dish—giving researchers a sharper lens on how these drugs hit the heart. The RNA sequencing added depth, peeling back layers of molecular shifts that echo clinical outcomes.

This could shift the game for drug testing. With heart tissue scarce and complex, this system offers a reliable stand-in, catching toxicities that might slip through other screens. As cancer treatments evolve, the question looms—how many hidden risks could this reveal before they reach patients? The heart slices are talking; scientists are listening.