When the heart is damaged, the muscle is starved of oxygen which kills off the heart muscle. The heart muscle cells are unable to regenerate, meaning that this damage is irreversible. Our focus is to use models of the heart in a dish to screen for new compounds that make the heart muscle regenerate without causing unintended growth of other cell types. Stem cells are crucial for this research, since they can be used to generate an unlimited supply of heart muscle cells that can be used to test hundreds of compounds.
Impact
Heart failure is one of the leading causes of death worldwide and has a poor prognosis for even those receiving first-line therapy, with a 5-year survival rate of 50%. Our research identifying new regenerative drugs will provide innovative therapeutic strategies for treating heart failure. Furthermore, our research using heart models from stem cells advances the current understanding of how heart muscle cells proliferate, paving the way for future regenerative therapies.
reNEW research
Initially, we screened 775 curated compounds in stem cell-derived simple models of the heart and looked at whether they helped encourage the heart muscle cells to regenerate. We then took videos of the cells while the drugs acted on them, and used machine learning assisted image analysis to figure out which drugs worked. We are now testing the top two compounds in more complex heart models and performing analysis to understand how these drugs are actually affecting the cells to enhance heart muscle growth.
Image description
This image shows a layer of heart cells generated from induced pluripotent stem cells, with a mix of heart muscle cells and heart fibroblasts (structural cells). The magenta cells are the heart muscle cells and the turquoise cells are the fibroblasts. These cells have been treated with one of the top hit compounds from our screen. Excitingly, the yellow shows the nuclei of regenerating cells, showing that the compound causes regeneration of the heart muscle cells specifically.
Credits
Dr Frankie Butera, Postdoctoral Researcher, Dr James McNamara, Associate Investigator, Ellen Keen, PhD Student, Porrello and Elliott Lab, reNEW Melbourne.
