16/05/2025

In pharmaceutical development, cardiotoxicity is a major reason why promising drug candidates fail — either in late-stage preclinical testing or after market approval. To address this challenge, a team from the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) and Hannover Medical School (MHH) has developed a more physiologically relevant cardiac organoid system.

Image: A man in a white lab coat looks through a microscope; Copyright: Fraunhofer ITEM

The tissue-like structure mimics human heart behavior and includes immune cells for improved drug testing.

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The new cardiac organoids are composed of approximately 2,000 cells, including heart muscle cells (cardiomyocytes), connective tissue cells (cardiac fibroblasts), vascular endothelial cells, and mesenchymal stem cells. All these are derived from human induced pluripotent stem cells (hiPSCs), which are reprogrammed from adult cells, such as those found in blood or connective tissue.

Elisa Mohr, a research scientist at Hannover Medical School and Fraunhofer ITEM, explains: “We differentiate induced pluripotent stem cells into cardiac muscle cells, fibroblasts and endothelial cells. Then we mix them with mesenchymal stem cells in a certain ratio and pipette the cell mix into an agarose mold that we place inside a Petri dish.” Within just four days, the cells self-organize into a spherical organoid about 200 micrometers in diameter that begins beating spontaneously — much like a tiny heart.

Cardiotoxicity and disease modeling

According to Prof. Christian Bär, research group leader at Fraunhofer ITEM, “Our model can essentially be used to test the cardiotoxicity of any medication.” This capacity makes it possible to detect heart-damaging effects much earlier and reduce costly late-stage drug failures.

In addition to evaluating cardiotoxicity, the organoids serve as models for a variety of cardiovascular diseases, including myocardial infarction, arrhythmias, and cardiac hypertrophy. Their ability to remain viable for at least 30 days makes them useful for studying chronic conditions and evaluating novel drug classes, such as RNA therapies.

Incorporating immune function

A key advancement in this model is the addition of macrophages, immune cells derived from hiPSCs. These “designer” immune cells, produced in scalable systems by Prof. Nico Lachmann at Fraunhofer ITEM, enhance the organoid’s physiological realism. “Adding the macrophages and thus incorporating immune competence into the cardiac organoid allows us to do research that is even closer to the actual human heart enabeling more reliable translational research,” Mohr notes.

MEDICA-tradefair.com; Source: Fraunhofer-Gesellschaft

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