Miniature human heart has potential to reshape drug testing

Human heart model

A tiny human heart model could potentially transform cardiovascular research and enable animal-free drug testing.

A team of researchers, led by the Hebrew University of Jerusalem (HU), has developed a self-paced, multi-chambered human heart model, approximately half the size of a rice grain.

“Integrating our complex human heart model with sensors allowed us to monitor critical physiological parameters in real-time, revealing intricate mitochondrial dynamics that drive cardiac rhythms,” said Professor Yaakov ‘Koby’ Nahmias, Director of the Hebrew University Alexander Grass Center for Bioengineering, and a Fellow of the American Institute for Medical and Biological Engineering (AIMBE). “This is a new chapter in human physiology.”

Professor Nahmias and his team created a highly accurate replica of a heart using human induced pluripotent stem cells (hiPSCs), which are derived from adult, non-reproductive cells that have been genetically reprogrammed.

“This is a new chapter in human physiology.”

The tiny model has multiple chambers, pacemaker clusters, epicardial membrane, and endocardial lining, with all features meticulously designed to mimic a human heart’s structure and functionality.

The heart model detected a new form of cardiac arrhythmia, distinct from those observed in traditional animal models, which will enable researchers to gain invaluable insights into the precise effects of pharmaceutical compounds on the human heart.

One of the most significant features is the new model heart’s ability to provide real-time measurements of essential parameters such as oxygen consumption, extracellular field potential, and cardiac contraction.

Screening 20,000 tiny human hearts

In the study, the researchers tested the heart model’s response to the chemotherapeutic drug mitoxantrone, commonly used to treat leukaemia and multiple sclerosis. Through these experiments, the researchers pinpointed how mitoxantrone induces arrhythmia by disrupting the heart’s electro-mitochondrial coupling. The team also discovered a potential solution by administering metformin, which showed promise for mitigating the drug’s adverse effects.

Partnering with Tissue Dynamics Ltd, a biotechnology company founded at Hebrew University by Professor Nahmias, the scientists have developed a robotic system that can screen 20,000 tiny human hearts in parallel for drug discovery applications.

“This miniature human heart model has the potential to reshape drug testing practices, advance our understanding of cardiovascular diseases, and ultimately contribute to a healthier and more sustainable future,” said the researchers.

Image credit: Tissue Dynamics

Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World

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