The Power of Muscle Stem Cells’ Mechanical Memory
by Micaela Harris
October 24, 2024
Muscle stem cells lie dormant in adult skeletal muscle ready to spring into action upon injury and repair muscle tissue. As we get older and the risk of disease increases, muscle stem cells become less effective in repairing muscle tissue. Why this occurs is not thoroughly understood.
A team of researchers at Stanford University, led by Christopher Madl, PhD, and Helen M. Blau, PhD examined whether muscle stem cells retain a memory of their past microenvironment (niche), and if their memory can be overridden in a recent study published in the Proceedings of the National Academy of Sciences. For these experiments the researchers used hydrogel biomaterials, substances that can mimic either the stiffness of healthy muscle or the increased stiffness characteristic of scarred muscle. Increased muscle stiffness arises from muscular dystrophy or aging and is due to increased connective tissue, or fibrosis. They investigators were also able to test how certain biochemical cues from the niche synergize with these physical cues to alter muscle stem cell behavior.
Immunofluorescence microscopy images show how the presence and abundance of specific markers (Pax7, MyoD, MyoG) that are characteristic of different phases of muscle stem cell behavior during muscle regeneration are influenced by hydrogel (niche) stiffness.
The team developed a new set of hydrogel materials that can be either stiffened or softened on demand via light exposure to mimic the changes in stiffness that occur in aging. By isolating muscle stem cells on initially stiff hydrogels that were eventually softened by light exposure, the investigators were able to evaluate how the cells react to the changing niche. They found that stem cells have a “mechanical memory” for the stiffness of the niche that is propagated to their progeny.
This study suggests that the stiff environment created by scarred muscle impedes the muscle stem cells’ ability to respond when triggered by injury to regenerate muscle tissue.
Future studies will focus on defining how this mechanical memory is conferred, and identifying therapeutic remedies that can overcome it.
Additional Stanford Cardiovascular Institute-affiliated investigators who contributed to this study include Yu Xin Wang, Colin Holbrook, Shiqi Su, Gwendoline Wicki, and Iris Flaig.
Dr. Christopher Madl
Dr. Helen Blau