Researchers at the Technical University of Munich (TUM) have successfully created a “mini-heart” known as an organoid. The organoid, made using pluripotent stem cells, emulates the development of a human heart in its earliest phases. It allows researchers to study the heart’s development during the early phase, which occurs about three weeks after conception and provides an opportunity to research diseases. With the ability to emulate heart conditions in organoids, drugs can be tested directly on them, which could reduce the need for animal experiments when developing drugs.

The organoid developed by the team is the first to contain heart muscle cells and cells of the outer layer of the heart wall, known as the epicardium. The epicardium is crucial to forming the heart’s chambers, and the researchers believe this development could lead to new treatment methods for heart attacks and other heart conditions. The organoids are half a millimeter in diameter and can contract like human heart chambers.

Additionally, the researchers have made several discoveries using organoids. They have found that precursor cells form on the seventh day of organoid development, responsible for forming the epicardium. These insights may also offer clues as to why the fetal heart can repair itself, which is almost absent in the heart of an adult human.

The researchers also showed that organoids could be personalized to investigate the illnesses of individual patients. Using pluripotent stem cells from a patient with Noonan syndrome, the researchers produced organoids that emulated the characteristics of the condition in a Petri dish. The team plans to use comparable personalized organoids to investigate other congenital heart defects. The research is a crucial area of focus at TUM, with other organoid projects in progress, including those related to the pancreas and brain.

The research was discussed in two studies and published in Nature Biotechnology and Nature Communications.

References

• Meier, A. B., Zawada, D., De Angelis, M. T., Martens, L. D., Santamaria, G., Zengerle, S., Nowak-Imialek, M., Kornherr, J., Zhang, F., Tian, Q., Wolf, C. M., Kupatt, C., Sahara, M., Lipp, P., Theis, F. J., Gagneur, J., Goedel, A., Laugwitz, K.-L., Dorn, T., & Moretti, A. (2023). Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease. Nature Biotechnology. https://doi.org/10.1038/s41587-023-01718-7
• TUM Research. (2023, April 4). A mini-heart in a Petri dish [Technical University of Munich]. TUM Research. https://www.tum.de/en/news-and-events/all-news/press-releases/details/mini-herzen-in-der-kulturschale
• Zawada, D., Kornherr, J., Meier, A. B., Santamaria, G., Dorn, T., Nowak-Imialek, M., Ortmann, D., Zhang, F., Lachmann, M., Dreßen, M., Ortiz, M., Mascetti, V. L., Harmer, S. C., Nobles, M., Tinker, A., De Angelis, M. T., Pedersen, R. A., Grote, P., Laugwitz, K.-L., … Goedel, A. (2023). Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools. Nature Communications, 14(1), 1722. https://doi.org/10.1038/s41467-023-36764-x