ART x SCIENCE 2024 #17
Connexin the dots; Cardiomyocyte maturation

Our group investigates cardiovascular diseases using stem cells differentiated into cardiomyocytes, the contractile cells of the heart. However, 2D hiPSC- derived cardiomyocytes resemble fetal-like cells, limiting their application in pathology, drug discovery, and regenerative medicine. We aim to overcome this by identifying the key drivers of cardiomyocyte maturation.

Body area Heart

Impact

Understanding cardiomyocyte maturation could help us develop more physiologically relevant 2D and 3D models. To enhance maturation, we culture cardiomyocytes with hiPSC-derived cardiac fibroblasts and endothelial cells in 3D microtissues. Connexin 43, a gap junctional protein, is upregulated in these microtissues. My research focuses on its role in the maturation of hiPSC-derived cardiomyocytes.

reNEW research

We successfully generated a connexin 43 knockout line and differentiated it into cardiomyocytes. Now, we are characterising the cardiomyocytes in 2D, and will soon create cardiac mircotissues utiling these cells. These microtissues drive the hiPSC- cardiomyocytes to a more mature phenotype, aiding in understanding connexin 43’s role in cardiomyocyte maturation.

Image description

We are able to differentiate hiPSC- derived cardiomyocytes lacking connexin 43 that still have well-organised sarcomeres.

Credits

Sanne Wiersma, PhD student, Milena Bellin lab, renew Leiden, The Netherlands.