Heart Slice Culture System Reliably Demonstrates Clinical Drug-Related Cardiotoxicity

The limited availability of human heart tissue and its complex cell composition are major limiting factors for reliable testing of drug efficacy, toxicity and understanding the mechanism. Recently, we developed a functional human and pig heart slice biomimetic culture system that fully preserves the viability and functionality of 300 micrometer heart slices for 6 days. Here, we validated the reliability of this culture system in delineating the mechanisms of known anti-cancer drugs that cause cardiomyopathy. We tested three different anti-cancer drug categories associated with cardiomyopathy (doxorubicin, trastuzumab, and sunitinib). Heart slices are not only able to demonstrate the expected toxicity of doxorubicin and trastuzumab similar to hiPS-derived-cardiomyocytes (hiPSC-CMs); but they are superior to hiPSC-CMs in demonstrating sunitinib cardiotoxicity which is not detectable in hiPSC-CMs at low concentrations. These results indicate that heart slice tissue culture models have the potential to become a reliable platform for testing drug toxicity and mechanistic behavior.