Existence Of Muscle-Building Stem Cells Points To Regenerative Therapies For Mus

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Existence Of Muscle-Building Stem Cells Points To Regenerative

Therapies For Muscular Disease

http://www.medicalnewstoday.com/medicalnews.php?newsid=72754

A new report in the June 1 issue of the journal Cell, a publication

of Cell Press, confirms the existence of some apparently uncommitted

stem cells amongst cells responsible for generating the bulging

biceps of body builders and the rippling abs of fitness buffs. The

findings could lead to new muscle-regenerating therapies - including

cell transplantation regimens and stem cell-replenishing drugs - for

people with various muscle-wasting diseases, including muscular

dystrophies. Ultimately, such treatments might also help keep people

strong as they age, according to the researchers.

A team led by Rudnicki of the Ottawa Health Research

Institute in Canada found that so-called satellite cells in muscle

actually include a mix of cells already committed to their muscular

fate and others that behave like more versatile stem cells. The

cells had widely been considered by scientists as a homogeneous

population of dedicated muscle progenitors. Moreover, Rudnicki's

team showed that injection of the " satellite stem cells " into the

muscles of mice successfully replenished the animals' regenerative

reservoir of cells.

" We've found that there are two types of satellite cell - 90% that

are already committed to becoming muscle and another 10% with

characteristics normally attributed to stem cells, " Rudnicki

said. " It's not been shown yet, but these muscle stem cells might

even have the capacity to make other tissues, such as bone and fat. "

" We've also shown that these satellite stem cells, when transplanted

into muscle, can repopulate the regenerative cell niche. This is a

very significant advance in our understanding of satellite cell

biology that will require us to rethink decades of research. It also

opens new avenues for therapeutic treatment of muscular diseases. "

Skeletal muscle fibers are essentially long, tubular cells, each of

which includes hundreds of nuclei. The fibers are surrounded by a

coating of collagen and other glycoproteins with satellite cells

sandwiched in between. First discovered in the 1960s, satellite

cells are known to be responsible for the growth, maintenance, and

repair of skeletal muscle after birth. The normally quiet

restorative cells spring into action in response to the stress of

weight-bearing or trauma.

Yet much about the mechanisms controlling satellite cells' identity

and development had remained uncertain, Rudnicki said. Earlier

studies had even suggested that satellite cells might originate from

muscle cells that had essentially regressed, or dedifferentiated, to

a more primitive developmental state.

In the new study, the researchers took a closer look at the

molecular profiles of satellite cells isolated from mouse muscle.

They showed that the satellite cells consist of two classes defined

by the activity or inactivity of a gene called Myf-5.

Moreover, that genetic difference gave rise to an important

distinction in the satellite cells - behavior. Cells without active

Myf-5 divide asymmetrically - a characteristic commonly seen among

stem cells. That lopsided cell division produced one " daughter " like

its parent, exhibiting a stem cell-like capacity for self renewal,

and another Myf-5 positive cell.

The researchers also showed that satellite cells in which Myf-5 was

switched on, when injected into the muscles of mice, continued down

the road toward becoming muscle. In contrast, transplantation of Myf-

5 negative cells " extensively contributed to the satellite cell

reservoir throughout the injected muscle. "

The findings led the researchers to conclude that satellite stem

cells could be used for direct transplantation into diseased muscle,

noting that molecular characterization of satellite stem cells

should lead to identification of markers enabling their prospective

isolation from human muscle tissue.

" Alternatively, " they added, " understanding the molecular regulation

of satellite stem cell symmetric versus asymmetric cell division

will lead to identification of biologics or small drugs that

specifically target the relevant pathway leading to satellite stem

cell expansion. "

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The researchers include Shihuan Kuang, Kazuki Kuroda, and Fabien Le

Grand of the Ottawa Health Research Institute in Ottawa, Canada and

A. Rudnicki of the Ottawa Health Research Institute and

University of Ottawa in Ottawa, Canada.

This work was supported by grants to M.A.R. from the Canadian

Institutes of Health Research, the National Institutes of Health,

Muscular Dystrophy Association, the Medical Institute,

and the Canada Research Chair Program. S.K. was supported by an

NSERC Postdoctoral Fellowship.