Cocktail for muscle renewal
A research team led by Sun Li, a member of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles, has identified a chemical cocktail that allows the production of a large number of muscle stem cells capable of self-renewal and giving rise to all types of skeletal muscle cells.
Muscle stem cells are responsible for the growth, repair and regeneration of muscles throughout a person's life. In adults, muscle stem cells remain inactive until they are called upon to respond to damage by self-replicating and creating all types of cells necessary to repair damaged tissue.
But the ability to regenerate is gradually lost with age; it can also be weakened by traumatic injuries and genetic diseases, for example, Duchenne muscular dystrophy.
Muscle stem cell-based therapy holds promising prospects for muscle recovery, but modern methods of generating patient-specific muscle stem cells can take months.
Li and his colleagues have identified a chemical cocktail – a combination of forskolin root extract and a small RepSox molecule that inhibits TGF-β cytokine receptors, which can effectively create a large number of muscle stem cells within 10 days. In studies on mice, researchers have demonstrated two potential ways in which the cocktail can be used as a therapy.
The first method uses dermal myogenic cells – skin cells that have the ability to turn into myocytes. The team found that treating myogenic skin cells with a chemical cocktail causes them to produce large numbers of muscle stem cells, which can then be transplanted into damaged tissue.
Muscle cells (red) obtained from stem cells using a new chemical cocktail are integrated into the damaged muscle (green) of an adult mouse.
Lee and his colleagues tested this approach on three groups of mice with muscle injuries: adult 8-week-old mice, old 18-month-old mice, and adult mice with a genetic mutation similar to the one that causes Duchenne muscular dystrophy in humans. Four weeks after transplantation, the muscle stem cells integrated into the damaged muscle and significantly improved muscle function in all three groups of mice.
For the second method, the researchers used nanoparticles to deliver a chemical cocktail to damaged muscle tissue. Nanoparticles made of absorbable polymer material provided a slow release of chemicals as they were destroyed.
This approach also led to muscle repair in all three groups of mice. When injected into the damaged muscle, the nanoparticles spread throughout the damaged area and released chemicals that activated the "dormant" muscle stem cells of mice.
Despite the effectiveness of both methods, an important advantage of the second is that it eliminates the need for cell cultivation in the laboratory – all processes of activation of muscle stem cells and muscle regeneration occur inside a living organism.
The researchers were amazed that the second method was effective even in old mice, because with age, the environment surrounding and supporting muscle stem cells loses its functions. Nanoparticles carrying a chemical cocktail allowed the muscle stem cells of old mice, despite the unfavorable microenvironment, to launch a reliable repair reaction.
In future studies, the research team will attempt to replicate the results on human cells and monitor the effects of therapy in animals for a longer period. The experiments should help determine whether any of these approaches can be used as a one-time treatment for patients with serious injuries.
The authors emphasize that the methods of muscle regeneration created by them are not able to eliminate the genetic defects that cause Duchenne muscular dystrophy and other genetic muscular dystrophy. However, they hope that muscle stem cells obtained from skin cells of a healthy donor can be transplanted into the muscles of patients with muscular dystrophy, for example, involved in breathing, and this will help increase survival and improve the quality of life of patients.
Article J.Fang et al. Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro is published in the journal Nature Biomedical Engineering.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCLA materials: Chemical cocktail creates new avenues for muscle stem cell therapies.