Scientists at the Technical University of Munich (TUM) have manipulated stem cells to mimic the development of the human heart, resulting in a sort of “mini-heart” known as an organoid. It will enable the study of the earliest development phase of the heart and further research on diseases.
Amazingly, the human heart starts forming less than three weeks after conception, when women are often unaware of their pregnancy. That’s one reason we still know little about how the heart is formed. And, findings from animal studies are, at best, only partially transferable to humans. However, the organoid developed at TUM could prove valuable to researchers.
The team, led by Alessandra Moretti, Professor of Regenerative Medicine in Cardiovascular Disease, developed a method for making a sort of “mini-heart” using pluripotent stem cells where around 35,000 cells are spun into a sphere in a centrifuge. Then, over several weeks, different signaling molecules are added to the cell culture under a fixed protocol. “In this way, we mimic the signaling pathways in the body that control the developmental program for the heart,” explains Alessandra Moretti. The group has now published its work in the journal Nature Biotechnology.
The resulting organoids are about half a millimeter in diameter. Although they do not pump blood, they can be stimulated electrically to contract like human heart chambers. Prof. Moretti and her team are the first researchers in the world to successfully create an organoid containing both heart muscle cells (cardiomyocytes) and cells of the outer layer of the heart wall (epicardium). The first organoids previously created only had cardiomyocytes and cells from the inner layer of the heart wall (endocardium).
“To understand how the heart is formed, epicardium cells are decisive,” says Dr. Anna Meier, the first author of the study. “Other cell types in the heart, for example, in connecting tissues and blood vessels, are formed from these cells. The epicardium also plays a very important role in forming the heart chambers.” The team has befittingly named the new organoids “epicardioids.”
Through the analysis of individual cells, the team has determined that precursor cells of a type only recently discovered in mice form around the seventh day of the development of the organoid. The epicardium forms from these cells. “We assume that these cells also exist in the human body — if only for a few days,” says Prof. Moretti.
These insights also offer clues as to why the fetal heart can repair itself, a capability almost entirely absent in the heart of an adult human. This understanding could help to find new treatment methods for heart attacks and other conditions.
The team also showed that the organoids can be used to investigate the illnesses of individual patients. For example, the researchers manufactured organoids that emulated characteristics of the condition in a Petri dish using pluripotent stem cells from a patient suffering from Noonan syndrome. Over the coming months, the team plans to use comparable personalized organoids to investigate other congenital heart defects. In addition, with the possibility of imitating heart conditions in organoids, medications could be tested directly on them in the future. “It is conceivable that such tests could reduce the need for animal experiments when developing drugs,” says Alessandra Moretti.
The team has registered an international patent for the process of creating heart organoids. The Epicardioid model is one of several organoid projects at TUM. Work groups from various departments and chairs will collaborate at the Center for Organoid Systems. They will conduct interdisciplinary research into pancreas, brain, and heart organoids with state-of-the-art imaging and cellular analysis to study the formation of organs, cancer, and neurodegenerative diseases and achieve progress for medicine with human 3D systems.
While this may not sound like much, it is a HUGE step that will hopefully lead to even bigger jumps in our understanding and abilities. It’s not hard to imagine being able to use something like this technique to grow new, specifically matched organs for people that need transplants. Does no more donor list, and no more rejection issues sound good to anyone?