Muscle Restored in mice by Purified Stem Cells

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Mice With Muscular Dystrophy Had Muscle Restored By Purified Stem

Cells

http://www.medicalnewstoday.com/articles/114730.php

By injecting purified stem cells isolated from adult skeletal muscle,

researchers have shown they can restore healthy muscle and improve

muscle function in mice with a form of muscular dystrophy. Those

muscle-building stem cells were derived from a larger pool of so-

called satellite cells that normally associate with mature muscle

fibers and play a role in muscle growth and repair.

In addition to their contributions to mature muscle, the injected

cells also replenished the pool of regenerative cells normally found

in muscle. Those stem cells allowed the treated muscle to undergo

subsequent rounds of injury repair, they found.

" Our work shows proof-of-concept that purified muscle stem cells can

be used in therapy, " said Amy Wagers of Harvard University, noting

that in some cases the stem cells replaced more than 90 percent of

the muscle fibers. Such an advance would require isolation of stem

cells equivalent to those in the mouse from human muscle, something

Wagers said her team is now working on.

Satellite cells were first described decades ago and have since

generally been considered as a homogeneous group, Wagers said. While

anatomically they look similar under a microscope, they nonetheless

show considerable variation in their physiology and function. In a

previous study, Wagers' 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 or SMPs.

In the new study, the researchers analyzed the stem cell and

regenerative properties of those SMPs. When engrafted into muscle of

mice lacking dystrophin, purified SMPs contributed to up to 94

percent of muscle fibers, restoring dystrophin expression and

significantly improving muscle structure and contractile function,

they report. (The dystrophin gene encodes a protein important for

muscle integrity. Mice lacking dystrophin, also known as mdx mice,

are a model for Duchenne Muscular Dystrophy, the most prevalent form

of muscular dystrophy.)

" 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, " the researchers said. " 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.

" 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. "

Wagers noted however that there may be complications in the delivery

of cell therapy in humans, particularly for those with conditions

influencing skeletal muscle throughout the body. Even so, the new

findings present an " opportunity to understand what happens [to these

regenerative cells] in disease and identify factors and pathways that

may boost their activity, " she said. " 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.