Extracellular Vesicles Spur Greater Muscle Regrowth in Old Mice
Cells signal to one another in a variety of means, and a large fraction of those signals pass back and forth in extracellular vesicles, small membrane-wrapped packages of molecules. An interesting use of extracellular vesicles is demonstrated here, delivering signals that provoke greater muscle regrowth in old mice than would otherwise be the case. Since it also works in young mice, this may be a basis for an enhancement therapy for people of all ages interested in building muscle. Extracellular vesicles can be harvested from cells and used in therapy more cost-effectively than the use of cell transplants. Thus much of the research community is engaged in various forms of the move from delivering cells to delivering vesicles harvested from those cells.
Scientists have developed a promising new method to combat the age-related losses in muscle mass that often accompany immobility after injury or illness. Physical therapy is often prescribed to promote healing after injury and immobility, she said. But studies show that muscle continues to deteriorate after the onset of exercise. Reactive oxygen species, a signal of inflammation and cellular dysfunction, accumulate in the muscles and impede the healing process.
In a previous study, researchers discovered that injections of support cells known as pericytes contributed to muscle recovery in young mice after a period of immobility. However, aged mice did not respond as well to the injections, and recovery was limited. In the new study, the team collected pericytes from the muscles of young, healthy mice and grew them in cell culture. They exposed the cells to hydrogen peroxide - a powerful oxidant that promotes the production of extracellular vesicles (EVs) containing factors that combat stress and enhance healing - and collected the EVs to use therapeutically.
The researchers injected their pericyte-derived EVs into the muscles of young and aged mice that had undergone a period of prolonged muscle immobility in one of their legs and were beginning to use those muscles again. The approach worked: The mice treated with the stimulated EVs recovered skeletal muscle fiber size in both young and aged mice. The study also revealed - for the first time - that EVs derived from muscle pericytes produced a variety of factors that may combat inflammation and oxidative stress.