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Mouse Study Suggests Hydrogel Matrix May Benefit Duchenne MD Patients.

ATLANTA, Ga., August 15, 2018 -- Injured muscles of elderly patients often take a long time to heal.

Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively.

A new method, tested in mice, may help change this.

Researchers at the Georgia Institute of Technology engineered 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 delivered MuSCs to injured, aged muscle tissue and boosted the healing process while protecting the stem cells from harsh immune reactions.

The method was also successful in mice with a muscle tissue deficiency that emulated Duchenne muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease.

Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient in part because the stem cells encounter an aggressive immune system reaction.

Any muscle injury is going to attract immune cells that would help muscle stem cells repair 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," said Young Jang of Georgia Tech's School of Biological Sciences.

Only between one and 20 percent of injected MuSCs make it to damaged tissue; those that do arrive weakened.

Also, some tissue damage makes any injection unfeasible, thus the need for new delivery strategies.

The new hydrogel protects the stem cells, which multiply and thrive inside the matrix. The gel is applied to 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 matrix forms, it ensnares the treatment for delivery and protects the payload from death or dissipation in the body.

Researchers can easily and reliably synthesize hydrogels and also custom-engineer them by tweaking their components, as the researchers did in this hydrogel.

It physically traps the muscle satellite cells, but the cells also grab onto chemical latches engineered into the gel.

This hydrogel's added latches, which bond with proteins protruding from stem cells' membranes, not only increase the cells' adhesion to the net but also hinder them from committing suicide.

Stem cells tend to kill themselves when they're detached and free-floating.

The chemical components and the cells are mixed in solution then applied to the injured muscle, where the mixture sets to a matrix-gel patch that glues the stem cells in place. The gel is biocompatible and biodegradable.

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.

In younger, healthier patients, muscle satellite cells are part of the natural healing mechanism.

Muscle satellite cells are resident stem cells in skeletal muscles. They live on muscle strands like specks, and they're key players in making new muscle tissue.

As people age, they lose muscle mass, and the number of satellite cells also decreases. The ones that are left get weaker.

"It's a double whammy," Jang said. "At a very advanced age, a patient stops regenerating muscle altogether."

The new system can introduce donor cells to enhance the repair mechanism in injured older patients. The researchers hope this will work in Duchenne muscular dystrophy patients.

Duchenne muscular dystrophy is surprisingly frequent. About one in 3,500 boys get it, and eventually get respiratory defects that lead to death.

"So we hope to be able to use this to rebuild their diaphragm muscles," Jang said.

If the method goes to clinical trials, researchers will likely have to work around the potential for donor cell rejection in human patients.

Citation: Woojin M. Han et al., Synthetic matrix enhances transplanted satellite cell engraftment in dystrophic and aged skeletal muscle with comorbid trauma. Science Advances, 2018; 4 (8): eaar4008 DOI: 10.1126/sciadv.aar4008


Contact: Young C. Jang,
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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Research News
Date:Sep 10, 2018
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