Research: heart and regeneration of damaged cells

22.05.2023

To uncover the mechanisms that can regenerate heart cells in zebrafish, researchers investigate the role of the LRRC10 protein structure in deciding whether heart muscle cells divide or continue towards maturation. Thanks to the collaboration with a group in Padua under Milena Bellin, researchers of the Hubrecht Institute published the study Interplay between calcium and sarcomeres directs cardiomyocyte maturation during regeneration in the journal ‘Science’.

Cardiovascular diseases, such as heart attacks, are a leading cause of death worldwide due to the limited regenerative capacity of the human heart. However, unlike humans, zebrafish have the remarkable ability to recover from cardiac damage. Researchers under Prof. Jeroen Bakkers of Hubrecht Institute in the Netherlands have used zebrafish to shed light on their regenerative success by uncovering a new mechanism that can switch heart muscle cells towards maturation during the regeneration process. The same mechanism was evolutionary conserved as it had a very similar effect on mouse and human heart muscle cells. Applying these findings to human heart muscle cells could help develop new therapies against cardiovascular diseases.

The regulation of calcium moving in and out within heart muscle cells is important for controlling heart contractions and can predict the maturity of the cell. As such, researchers developed a technique for which thick slices of injured zebrafish hearts were cultured outside the body. This allowed them to perform live imaging on the movement of calcium in heart muscle cells. They found that after the heart muscle cells divide, the rate of calcium moving in and out changed over time. With the collaboration led by Milena Bellin - University of Padua Department of Biology, Veneto Institute of Medicine Molecular, and Leiden University Medical Center – researchers studied cardiomyocytes generated from human pluripotent stem cells grown in the laboratory.  Experiments conducted at the Leiden University Medical Center by Giulia Campostrini, a researcher under Milena Bellin and Christine Mummery proved that LRRC10 plays a role in the maturation of human cardiac cells.

The study demonstrates that LRRC10 has the ability to drive the maturation of cardiac muscle cells by controlling their calcium management. This could help scientists address the mammalian heart's lack of regenerative capacity by transplanting lab-grown heart muscle cells into damaged hearts. While this potential therapy is promising, results have shown that lab-grown cells lack the maturity needed to communicate with the rest of the heart, thus leading to cardiac arrhythmias.

Therefore, LRRC10 could, by making cultured heart muscle cells more representative of the human situation, thus improve the chances of developing successful new treatments against cardiovascular diseases.