A UCLA-led research team has identified a chemical cocktail that enables it to produce large numbers of muscle cells, which can self-renew and cause all types of skeletal muscle cells.
The progress could lead to the development of gas cell-based therapies for muscle loss or damage due to injury, age or disease. The research was published in Nature Biomedical Engineering.
Muscle stem cells are responsible for muscle growth, repair and regeneration after a lifelong injury. In fully grown adults, muscle stem cells are questionable -; they become inactive until they are called upon to deal with an injury by reproducing themselves and creating all the cell types necessary to repair damaged tissue.
But that renewable capacity decreases as people age; it can also be exacerbated by traumatic injuries and genetic diseases such as Duchenne muscular dystrophy.
Muscle gas-based therapies show a great deal of promise for promoting muscle regeneration, but conventional methods for generating specific muscle stem cells can take patients months. “
Song Li, Study Lead Author and Member of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA
Li and his colleagues noted a chemical cocktail -; combination of the root extract forskolin and the small molecule RepSox -; that can effectively form large numbers of muscle cells within 10 days. In mouse studies, the researchers showed two possible ways to use the cocktail as a remedy.
The first method uses cells found in the skin called dermal myogenic cells, which have the potential to become muscle cells. The team found that manipulating dermal myogenic cells with the chemical cleavage led them to produce large numbers of muscle cells, which could then be transplanted. into wound material.
Li’s team tested this approach in three groups of mice with muscle injury: adult mice (8-weeks), elderly mice (18 months) and adult mice with a genetic mutation similar to the one caused by Duchenne in the people.
Four weeks after the cells were transplanted, the muscle stem cells were folded into the damaged muscle and muscle activity was enhanced in all three groups of mice.
For the second method, Li’s team used nanoparticles to deliver the chemical cocktail to damaged muscle tension. The nanoparticles, which are about one hundredth the size of a grain of sand, are made of the same material as removable surgical strips, and are designed to slowly release the chemicals during fracture down.
The second approach also produced a strong repair response in all three mouse types. When inserted into injured muscles, the nanoparticles migrated throughout the injured area and released the chemicals, which activated quiescent muscle gas cells to begin to divide.
While both methods were successful, the main advantage of the latter was that it eliminated the need for growth cells in the laboratory -; activity and regeneration of whole cell gas takes place inside the body.
The team was particularly surprised to find that the second method was effective even in older mice, regardless of how animals age, the surrounding environment and taking support muscle cells so effectively.
“Our chemical cocktail enabled muscle cells in older mice to overcome their harsh environment and trigger a strong repair response,” said Li, who is also chair of bioengineering at UCLA Samueli School of Engineering and senior professor of medicine at UCLA’s David Geffen School of Medicine.
In future studies, the research team will try to reproduce the results in human cells and monitor the effect of the treatment in animals for a longer period of time. The tests should help determine if one approach could be used as a one-time treatment for patients with severe injuries.
Li noted that one approach would not fix the genetic defect caused by Duchenne or other genetic muscular dystrophies. However, the team notes that muscle stem cells generated from healthy donor skin cells could be transplanted into a muscular dystrophy patient’s muscle -; as in the lungs -; which could extend their life and improve their quality of life.
Source:
University of California – Los Angeles Health Sciences