Stem cell derived organoids tend to be similar to embryonic tissue, so we are aiming to develop more functionally mature muscle organoids. Mature muscle fibres will better represent muscle we see in the human body, meaning they are stronger, and will properly respond to external signals. Our research aims to determine which factors are important for getting muscle to be as mature as possible.
Impact
Recent advances in the creation of muscle organoids have shown great promise in modelling muscle disease. However, due to the functional immaturity of these tissues, we cannot properly predict how drugs will act on mature muscle. Our research will allow us to create tissues that are more mature, providing a better model for investigating muscle disease, and more accurate drug discovery.
reNEW research
The Mills Lab have developed large-scale functional skeletal muscle organoids which can produce contractile force upon stimulation. We have developed culture conditions which improve their functional outputs, including contractile force, and increased expression of markers known to be associated with muscle maturity. We use this system to investigate muscle disease with known genetic mutations.
Image description
The image shows a bundle of muscle fibres, seen in blue, from a muscle organoid. ACTN2, shown in red, acts as a proxy for muscle fibre maturity, in tandem with GLUT4, shown in magenta. Note how different fibres within the bundle show different levels of maturity as determined by the combinations of these stains. Nuclei of muscle fibres and surrounding supporting cells are shown in yellow.
Credits
Callum Dark, Senior Research Officer, Richard Mills Lab, reNEW Melbourne.
