A team on the Technical University of Munich (TUM) has induced stem cells to emulate the event of the human heart. The result’s a form of “mini-heart” referred to as an organoid. It would permit the study of the earliest development phase of our heart and facilitate research on diseases.
The human heart starts forming roughly three weeks after conception. This places the early phase of heart development in a time when women are sometimes still unaware of their pregnancy. That’s one reason why we still have little knowledge of many details of how the center is formed. Findings from animal studies will not be fully transferable to humans. An organoid developed at TUM could prove helpful to researchers.
A ball of 35,000 cells
The team working with Alessandra Moretti, Professor of Regenerative Medicine in Cardiovascular Disease, has developed a technique for making a form of “mini-heart” using pluripotent stem cells. Around 35,000 cells are spun right into a sphere in a centrifuge. Over a period of several weeks, different signaling molecules are added to the cell culture under a hard and fast protocol. “In this fashion, we mimic the signaling pathways within the body that control the developmental program for the center,” explains Alessandra Moretti. The group has now published its work within the journal Nature Biotechnology.
First-ever “epicardioids”
The resulting organoids are about half a millimeter in diameter. Although they don’t pump blood, they may be stimulated electrically and are able to contracting like human heart chambers. Prof. Moretti and her team are the primary researchers on this planet to successfully create an organoid containing each heart muscle cells (cardiomyocytes) and cells of the outer layer of the center wall (epicardium). Within the young history of heart organoids – the primary were described in 2021 – researchers had previously created only organoids with cardiomyocytes and cells from the inner layer of the center wall (endocardium).
To know how the center is formed, epicardium cells are decisive. Other cell types in the center, for instance in connecting tissues and blood vessels, are formed from these cells. The epicardium also plays a vital role in forming the center chambers.” The team has appropriately named the brand new organoids “epicardioids”.
Dr. Anna Meier, first creator of the study
Latest cell type discovered
Together with the strategy for producing the organoids, the team has reported its first latest discoveries. Through the evaluation of individual cells they’ve determined that precursor cells of a kind only recently discovered in mice are formed across the seventh day of the event of the organoid. The epicardium is formed from these cells. “We assume that these cells also exist within the human body – if just for a couple of days,” says Prof. Moretti.
These insights may additionally offer clues as to why the fetal heart can repair itself, a capability almost entirely absent in the center of an adult human. This data could help to search out latest treatment methods for heart attacks and other conditions.
Producing “personalized organoids”
The team also showed that the organoids may be used to analyze the illnesses of individual patients. Using pluripotent stem cells from a patient affected by Noonan syndrome, the researchers produced organoids that emulated characteristics of the condition in a Petri dish. Over the approaching months the team plans to make use of comparable personalized organoids to analyze other congenital heart defects.
With the opportunity of emulating heart conditions in organoids, drugs may very well be tested directly on them in the longer term. “It’s conceivable that such tests could reduce the necessity for animal experiments when developing drugs,” says Alessandra Moretti.
Organoid research is a key research area at TUM
The researchers have registered a global patent for the technique of creating heart organoids. The Epicardioid model is one in all several organoid projects at TUM. On the Center for Organoid Systems work groups from various departments and chairs will collaborate. They may conduct interdisciplinary research into pancreas, brain and heart organoids with state-of-the-art imaging and cellular evaluation to check the formation of organs, cancer and neurodegenerative diseases and achieve progress for medicine with human 3D systems.
Source:
Technical University of Munich (TUM)
Journal reference:
Meier, A. B., et al. (2023). Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease. Nature Biotechnology. doi.org/10.1038/s41587-023-01718-7.