Autofluorescence to select the best muscle stem cells
In certain muscle diseases, such as Duchenne muscular dystrophy, or in cases of age-related muscle loss (sarcopenia), the muscle's natural ability to regenerate is severely impaired. Identifying and exploiting cells capable of restoring muscle tissue represents a major challenge for research and development of new therapeutic strategies.
Natural muscle stem cells, satellite cells and their derivatives, myoblasts, cannot be directly isolated and used for therapeutic purposes because their numbers are limited and their expansion in the laboratory considerably reduces their regenerative potential. Human muscle reserve cells (MuRCs), produced in vitro, offer a promising avenue, particularly because they can be generated in sufficient quantities for therapeutic applications. However, these populations are heterogeneous and the selection of the most effective cells relies on invasive methods that compromise their viability.
Autofluorescence, a natural marker...
In a recent study published in the journal Stem Cell Research & Therapy, Dr Thomas Laumonier's research team shows that an intrinsic property of human muscle reserve cells, their autofluorescence, makes them easy to identify without altering their integrity.
Human muscle reserve cells (left) exhibit intrinsic autofluorescence that differentiates them from primary human myoblasts (right).
... to identify the most "dormant" stem cells
The most autofluorescent human muscle reserve cells are those that strongly express the transcription factor Pax7, an indicator of a state of deep quiescence. It is precisely these most "dormant" muscle stem cells that are the most promising.
The most autofluorescent muscle stem cells have a deeper level of quiescence.
To test this potential, the researchers transplanted human muscle reserve cells with high and low autofluorescence into mice. These cells survived, contributed to the formation of new muscle stem cells, and effectively promoted regeneration after muscle injury.
Next steps
Ultimately, this work could contribute to the development of safer and more effective regenerative medicine strategies for treating certain muscle diseases. However, the research team found that not all highly autofluorescent human muscle reserve cells are as "dormant" as hoped. They are now working to modulate their metabolism in order to increase the proportion of cells in deep quiescence, thereby optimising muscle regeneration.