Lab grown, self-sustainable muscle cells repair muscle injury and
disease, mouse study shows

Date:
April 20, 2022
Source:
Johns Hopkins Medicine
Summary:
In proof-of-concept experiments, scientists say they have
successfully cultivated human muscle stem cells capable of renewing
themselves and repairing muscle tissue damage in mice, potentially
advancing efforts to treat muscle injuries and muscle-wasting
disorders in people.



FULL STORY ==========================================================================
In proof-of-concept experiments, Johns Hopkins Medicine scientists
say they have successfully cultivated human muscle stem cells capable
of renewing themselves and repairing muscle tissue damage in mice,
potentially advancing efforts to treat muscle injuries and muscle-wasting disorders in people.


==========================================================================
A report on the experiments was published April 7 in Cell Stem Cell.

To make the self-renewing stem cells, the scientists began with
laboratory- grown human skin cells that were genetically reprogrammed to
a more primitive state in which the cells have the potential to become
almost any type of cell in the body. At this point, the cells are known
as induced pluripotent stem (IPS) cells, and they are mixed with a
solution of standard cell growth factors and nutrients that nudge them
to differentiate into specific cell types.

In the laboratory, scientists have long been able to transform IPS cells
into various types of cells, including skin and brain cells. What has
been far more difficult, say the researchers, is the ability to turn
IPS cells into self- renewing stem cells for a particular organ.

The research team, led by Gabsang Lee, Ph.D., D.V.M., professor of
neurology and member of the Institute of Cell Engineering at Johns
Hopkins Medicine, coaxed IPS cells to turn into muscle stem cells using
a nutrient-rich broth.

Further studies are planned, Lee says, to examine the recipe further to determine which ingredients may be key to brewing the muscle stem cells.

Lee is co-founder of Vita Therapeutics Inc., a Baltimore, Maryland-based
cell engineering company, that hopes to bring muscle stem cell treatments
to market for muscle wasting disorders, including muscular dystrophy. He cautions that such stem cell therapies are not yet available.



==========================================================================
In proof-of-concept experiments with mice, the research team sought to determine where the newly developed cells would migrate in living animals,
and if they could repair damaged tissue.

The team reported that when they injected the muscle stem cells into
the mouse muscles, the cells moved to an area of the muscles known as
the niche, where other natural muscle stem cells are typically found,
and stayed there for more than four months.

The research team then used two different methods to determine if the
muscle stem cells would repair damaged tissue.

In one method, the researchers transplanted the muscle stem cells into
mice genetically engineered and bred without an immune system to avoid rejection of the transplanted cells. They then exposed the animals to
a muscle-degrading toxin and radiation to eliminate muscle stem cells
already existing within the mouse.

At the site of the toxin and radiation damage in the muscle tissue, the researchers found that the transplanted human muscle stem cells developed
into myoblasts, a kind of muscle construction cell that repairs damage by fusing together and developing the microfibers that characterize normal
muscle. They also found that some of the transplanted human muscle stem
cells migrate to the niche and behave like muscle stem cells naturally
found within the mouse.



==========================================================================
In a second set of experiments, the researchers transplanted the muscle
stem cells into mice genetically engineered with a mutation in the
dystrophin gene, which results in Duchenne muscular dystrophy, a muscle
wasting disorder in mice and humans.

The researchers found that transplanted muscle stem cells traveled to
the muscle niche area. Over several months, tests showed the transplanted
mice were able to run twice as far on mini treadmills than untreated mice,
a measure of muscle strength.

"These muscle stem cells could potentially be developed as treatments
for many types of muscle disorders," says Lee.

The research team plans to study the use of the cells in mouse models
of other muscle-related conditions for their potential use in sports
medicine, trauma, and age-related muscle loss.

Support for this research was provided by the National Institutes of
Health (R01NS093213, R01-AR076390, K01-AR074048, R01AR070751), the
Maryland Stem Cell Research Fund, the Maryland Stem Cell Fellowship,
Vita Therapeutics, the Muscular Dystrophy Association, the Peter and
Carmen Lucia Buck Foundation, the American Heart Association Predoctoral Fellowship, an American Heart Association Career Development Award, an
American Heart Association Established Investigator Award, and National Research Foundation of Korea grants.

Under a license agreement between Vita Therapeutics and The Johns
Hopkins University, Lee, Kathryn R. Wagner, and the University are
entitled to royalty distributions related to technology described in
the study discussed here. Vita Therapeutics provided partial support
for this study. Lee, Wagner, and Peter Andersen are co-founders of Vita Therapeutics and hold equity in the company.

Other scientists who contributed to the research include Sunny (Congshan)
Sun, Suraj Kannan, In Young Choi, HoTae Lim, Hao Zhang, Grace Chen, Nancy Zhang, Seong-Hyun Park, Carlo Serra, Shama Iyer, Thomas Lloyd, Chulan Kwon
and Peter Andersen of Johns Hopkins; Richard Lovering of the University of Maryland School of Medicine (now at the National Institutes of Health);
Su Bin Lim of the Ajou University School of Medicine in South Korea;
and Congshan Sun and Kathryn Wagner, formerly of Johns Hopkins and the
Kennedy Krieger Institute and now at Vita Therapeutics and F. Hoffman
La-Roche Inc., respectively.


========================================================================== Story Source: Materials provided by Johns_Hopkins_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Congshan Sun, Suraj Kannan, In Young Choi, HoTae Lim, Hao Zhang,
Grace S.

Chen, Nancy Zhang, Seong-Hyun Park, Carlo Serra, Shama R. Iyer,
Thomas E.

Lloyd, Chulan Kwon, Richard M. Lovering, Su Bin Lim, Peter Andersen,
Kathryn R. Wagner, Gabsang Lee. Human pluripotent stem cell-derived
myogenic progenitors undergo maturation to quiescent satellite
cells upon engraftment. Cell Stem Cell, 2022; 29 (4): 610 DOI:
10.1016/ j.stem.2022.03.004 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220420151643.htm

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