A muscle stem cell with a morphology associated with quiescence (yellow). Image credit: Erik Jacques (CC BY 4.0)
When our muscles are injured, stem cells in the tissue are activated to start the repair process. However, when there is no damage, these cells tend to stay in a protective, dormant state known as quiescence. If quiescence is not maintained, the stem cells cannot properly repair when the muscle is damaged. This happens in old age, when a proportion of the cells remain semi-activated, and become depleted. However, researchers still do not fully understand how quiescence is regulated. This is partly because in order to study quiescence, live animals must be used, because muscle stem cells immediately come out of quiescence when they are removed from muscle tissue.
To overcome this experimental limitation, Jacques et al. developed a new method to study muscle stem cells by transferring them from mice into three-dimensional engineered muscle tissue grown in the lab. This tissue is made by infiltrating the pores of teabag paper with muscle progenitor cells, which then fuse with one another to make a thin muscle that contains three layers of contractile muscle cells. Introducing muscle stem cells from young healthy animals into this engineered muscle tissue allowed them to return to a quiescent-like state and to remain in that state for at least a week. Cells from older animals could also be returned to dormancy if they were chemically treated after placing them in the engineered muscle tissue.
The approach works in a miniaturized fashion, with each engineered tissue requiring less than one per cent of the muscle stem cells collected from each mouse. This allows 100 times as many experiments compared to the current methods using live animals.
This system could help researchers to study the genetic and chemical influences on muscle stem cell quiescence. Further understanding in this area could lead to treatments that restore healing abilities in older muscle tissue.
