Researchers examined a molecular matrix, a hydrogel, to deliver muscle stem cells called muscle satellite cells (MuSCs) directly to injured muscle tissue in patients whose muscles don't regenerate well. In lab experiments on mice, the hydrogel successfully delivered MuSCs to injured, aged muscle tissue and boosted the healing process while protecting the stem cells from harsh immune reactions.
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method may help change this. The study was published in the journal Science Advances.
The method was also successful in mice with a muscle tissue deficiency that emulated Duchene muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease.
Inflammation war zone
Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient, in part because the stem cells encounter an immune system on the warpath. Any muscle injury is going to attract immune cells.
Typically, this would help muscle stem cells repair the damage. But in aged or dystrophic muscles, immune cells lead to the release of a lot of toxic chemicals like cytokines and free radicals that kill the new stem cells.
Only between 1 and 20 percent of injected MuSCs make it to damaged tissue, and those that do, arrive there weakened. Also, some tissue damage makes any injection unfeasible, thus the need for new delivery strategies.
Our new hydrogel protects the stem cells, which multiply and thrive inside the matrix. The gel is applied to the injured muscle, and the cells engraft onto the tissues and help them heal. Hydrogels often start out as water-based solutions of molecular components that resemble crosses, and other components that make the ends of the crosses attach to each other.
When the components come together, they fuse into molecular nets suspended in water, resulting in a material with the consistency of a gel. If stem cells or a drug are mixed into the solution, when the net, or matrix, forms, it ensnares the treatment for delivery and protects the payload from death or dissipation in the body.
The stem cells keep multiplying and thriving in the gel after it is applied. Then the hydrogel degrades and leaves behind the cells engrafted onto muscle tissue the way natural stem cells usually would be.
Stem cell breakdown
In younger, healthier patients, muscle satellite cells are part of the natural healing mechanism. Muscle satellite cells are resident stem cells in your skeletal muscles. They live on muscle strands like specks, and they're key players in making new muscle tissue.
Duchene Muscle Dystrophy
With this system we engineered, we think we can introduce donor cells to enhance the repair mechanism in injured older patients. We also want to get this to work in patients with Duchene muscular dystrophy.
Duchene muscular dystrophy is surprisingly frequent. About 1 in 3,500 boys get it. They eventually get respiratory defects that lead to death, so we hope to be able to use this to rebuild their diaphragm muscles. If the method goes to clinical trials, researchers will likely have to work around the potential for donor cell rejection in human patients.