Purified Stem Cells Offer New Hope in Muscular Dystrophy

Harvard University researchers have shown through mice studies that it may be possible to restore healthy muscle among those afflicted by muscular dystrophy by injecting purified stem cells isolated from adult skeletal muscle.

The researchers have revealed that they derived the muscle-building stem cells from a larger pool of so-called satellite cells, which normally associate with mature muscle fibres and play a role in muscle growth and repair.

They say that besides their contributions to mature muscle, the injected cells also replenished the pool of regenerative cells normally found in muscle.

According to them, those stem cells enabled the treated muscle to undergo subsequent rounds of injury repair.

"Our work shows proof-of-concept that purified muscle stem cells can be used in therapy," said Amy Wagers of the university, noting that in some cases the stem cells replaced more than 90 percent of the muscle fibres.

She says that her team is now trying to device ways to isolate such stem cells from human muscle as would be equivalent to those in the mice they studied, in order to realise a therapy based on their findings.

Wagers says that in a previous study her team had identified a set of five markers that characterize the only subset of satellite cells responsible for forming muscle, which they also refer to as skeletal muscle precursors (SMPs).

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The researcher says that she and her colleagues analysed the stem cell and regenerative properties of those SMPs in their latest study.

She says that upon being engrafted into muscle of mice lacking dystrophin, purified SMPs contributed to up to 94 percent of muscle fibres, restoring dystrophin expression and significantly improving muscle structure and contractile function.

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"Importantly, high-level engraftment of transplanted SMPs in mdx animals shows therapeutic value-restoring defective dystrophin gene expression, improving muscle histology, and rescuing physiological muscle function. Moreover, in addition to generating mature muscle fibers, transplanted SMPs also re-seed the satellite cell niche and are maintained there such that they can be recruited to participate in future rounds of muscle regeneration," the researchers said.

"Taken together, these data indicate that SMPs act as renewable, transplantable stem cells for adult skeletal muscle. The level of myofiber reconstitution achieved by these myogenic stem cells exceeds that reported for most other myogenic cell populations and leads to a striking improvement of muscle contraction function in SMP-treated muscles. These data thus provide direct evidence that prospectively isolatable, lineage-specific skeletal muscle stem cells provide a robust source of muscle replacement cells and a viable therapeutic option for the treatment of muscle degenerative disorders," they added.

Wagers concedes that there may be complications in the delivery of cell therapy in humans, particularly for those with conditions influencing skeletal muscle throughout the body.

She, however, adds that the new findings still present an "opportunity to understand what happens (to these regenerative cells) in disease and identify factors and pathways that may boost their activity."

"We may get a handle on drugs that could target muscle impairment" not only in those with muscular dystrophies, but also in elderly people suffering from the muscle wasting that comes with age, she said.

Source-ANI
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