How do cells grow out to be heart cells? And how do these cells ripe to being fully functional heart cells? Researchers University of Twente and Radboud University hope to answer these questions. ZonMw awards the research of molecular regulation mechanisms from human heart cells a TOP grant of 675.000 euros.
Cardiovascular disease is the leading cause of death in the western world. Ten years ago it became possible to reprogram patient cells (for example cells obtained from skin or blood) to human induced pluripotent stem cells (hPSC). These cells can be differentiated into a range of somatic cell types, including cardiomyocytes (heart cells). However these cells have a variety of cardiac identities that are more similar to fetal than to adult heart muscle cells.
Robert Passier, professor of Applied Stem Cell Technologies at the University of Twente, and Gert Jan Veenstra, professor of Molecular Developmental Biology at Radboud University, have been awarded a grant of 675,000 euro for the identification of molecular regulatory pathways for specification and maturation of human cardiac subtypes. In this project the researchers will collaborate with medical centres in Leiden (LUMC) and Amsterdam (AMC, VUmc).
How to direct heart cells to correct identity
‘It is important to understand how to create the different types of cell from the heart and how we can let them mature, which will allow us to compare them to cells in a mature heart,’ explains Robert Passier. For the first time the genetic, epigenetic and molecular mechanisms that are important for differentiation and maturation of cardiomyocyte subtypes will be studied extensively. ‘To achieve this, we will map the differentiation process of the different cell types using ‘single cell’ approaches. We use these to identify individual differences between cells. In addition, we will determine the epigenetic changes, changes in the gene function without changing the DNA sequence, during cell differentiation’, as explained by Gert Jan Veenstra.
The project is expected to make an important contribution to the understanding, modeling and treatment of heart disease. Passier: ‘More knowledge on the differentiation and maturation of humane muscle cells in the heart will eventually lead to improved in vitro models to study heart diseases and to test medicines. We also expect that this knowledge will help to decrease the number of animals used for research.’
The ZonMW TOP programme offers strong research groups in biomedical and healthcare research the opportunity to engage in new, risky lines of research. It therefore also supports combinations of disciplines and research groups. TOP projects are above all expected to deepen scientific understanding (enhance knowledge, form models and theories). ZonMw regards this unconstrained boost to science as the ideal way to drive innovation in the long term.
This news item has been taken over with permission from the Radboud University
Picture: Rikkert Harink