July 24, 2024
First Multi-Chamber Heart Organoids Unravel Human Heart Development and Disease

First Multi-Chamber Heart Organoids Unravel Human Heart Development and Disease

A groundbreaking study published in the journal Cell reveals the development of a multi-chamber organoid that mimics the intricate structure of the human heart. This significant breakthrough provides scientists with a physiological model to advance drug development, toxicology studies, and improve understanding of heart development and disease.

Heart disease remains the leading cause of death worldwide, claiming the lives of 18 million people annually. Unfortunately, the development of new therapies is limited due to the lack of a comprehensive model of the human heart. Furthermore, congenital heart defects affect one in every 50 babies born, with limited treatment options available.

The research team at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences, led by Sasha Mendjan, has created a multi-chamber organoid model that encompasses all major regions of the human heart. This model allows researchers to study both cardiac disease and development.

In a groundbreaking study conducted in 2021, the IMBA team developed chamber-like organoids known as Cardioids, formed from human induced pluripotent stem cells. These Cardioids successfully replicated the development of the heart’s left ventricular chamber during the early stages of embryogenesis. While this was a significant achievement, most adult diseases primarily affect the left ventricle, whereas congenital defects often impact other essential regions of the heart involved in establishing and maintaining circulation.

Building upon their previous work, the researchers at IMBA pursued the development of multi-chamber Cardioids. They first derived organoid models of each individual developing heart structure and then co-developed them to observe if a coordinated beating pattern could occur, similar to the early human heart.

Surprisingly, the researchers observed that an electrical signal spread from the atrium to the left and right ventricular chambers, replicating the process seen during early fetal heart development in animals. This marks the first time this fundamental process has been observed in a human heart model with all its chambers.

While the previous Cardioid model allowed for the study of chamber shape and tissue organization, the new multi-chamber Cardioids provided a deeper understanding of regional gene expression differences and specific chamber contraction patterns. The intricate communication between the chambers was also analyzed.

The multi-chamber Cardioids not only contribute to studying heart development but also allow researchers to investigate chamber-specific defects. In a proof-of-principle experiment, the Mendjan team established a screening platform to study how known teratogens (substances that can cause birth defects) and mutations affect multiple heart organoids simultaneously. Notably, teratogens such as thalidomide and retinoid derivatives, as well as specific mutations in cardiac transcription factor genes, induced severe compartment-specific defects in the heart organoids.

The multi-chamber Cardioids also have potential applications in toxicology studies and the development of drugs with heart chamber-specific effects. For instance, atrial arrhythmias, a common condition, currently lack effective treatments due to the absence of comprehensive models that replicate the coordinated working of all regions of the developing heart.

The future use of heart organoids derived from patient-derived stem cells may offer valuable insights into developmental defects and potential treatments or preventive measures. The IMBA research group plans to utilize multi-chamber heart organoids to further explore the growth and regenerative potential of the heart.

HeartBeat.bio AG, a spin-off company of IMBA co-founded by Sasha Mendjan, has been granted an exclusive license to the multi-chamber cardiac organoid technology. This licensing agreement will allow HeartBeat.bio to expand its portfolio of disease models and enhance its cardiac drug discovery pipeline using the fully automated and integrated human 3D drug discovery platform based on IMBA’s left-ventricular Cardioid technology.

This groundbreaking research presents a major leap forward in understanding heart development and disease. The creation of the multi-chamber heart organoid model opens up new avenues for drug development, toxicology studies, and personalized treatments for cardiac conditions.

 

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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it