








































Abstract: Genetic disorders affect many people, and muscular dystrophy is a disorder 
that can greatly decrease the quality of life.  Finding treatment to stop or prevent the loss 
of muscle function by the dystrophin protein is a top goal for scientists in this field.  The 
treatment involves stem cell transplantation by intravenous injection, or local muscle in-
jections.  Various stem cells are under consideration, with analysis focusing on the specific 
stem cells’ effectiveness and ability to be used as a treatment.

Aisthesis      Volume 7,  201638

Muscular Dystrophy: Stem Cell Therapy
by Caitlin Pederson

Introduction: Muscular Dystrophy
 Muscular dystrophy is a genetic disorder, with 
approximately 30 variations of the inherited disease.1,3  
All of the various forms of this disease can result in 
both muscle weakness and muscle loss.  The variations 
can differ in their onset, either occurring during infancy, 
childhood, or middle to late thirties, but all are a 
genetic disease with similar symptoms.1,3 Depending 
on the specific variation of this genetic disease, 
symptoms can be mild with only physical therapy 
needed as a treatment, or symptoms can be severe, 
potentially causing disability and early death. This 
genetic disease is different from other sicknesses in 
that there is currently no way to treat it because it is 
coded into the person’s DNA, the instructions for a 
person’s life.  
 The most common variation of muscular 
dystrophy, Duchenne muscular dystrophy (DMD), 
is the result of a mutation of a specific gene in the 
genetic code.  This gene codes for a 427 kD cytoskeletal 
protein called dystrophin, believed to be the largest 
gene in the human genome.2  The mutation of the 
gene dystrophin is often caused by an accidental 
insertion or deletion of a nucleotide in the DNA 
causing a frameshift, or point mutation, which causes 
an error in the protein formation.2  The mutation 
causes dystrophin to be either completely lacking 
from the muscle cell, or functioning incorrectly.  With 
dystrophin not working correctly, muscles begin to 
weaken and deteriorate.  Dystrophin acts as the shock 

absorbers for muscle cells and prevents fibre damage 
of the muscles; without this protein the muscles wear 
out.2  To cure the disease the cells would need to be 
repaired, so a treatment would need to be found that 
can correct the dystrophin protein and its complex.
 There are several different treatments for muscular 
dystrophy.  The simplest therapies for the disease 
involve keeping the muscles mobile and trying to 
promote an upright posture.  Braces are used to keep 
the spine and joints in desired locations with the 
muscles functioning in the correct manner.1   Surgeries 
may also be performed as treatment to release tendons 
that tighten as the disease progresses.1  Medications, 
belonging to a group called corticosteroids, are being 
used to slow the effect of DMD.1  Gene replacement 
therapy is a treatment that uses viruses or plasmids 
to deliver dystrophin gene sequences to cells with 
incorrect sequences, but the treatment is in the 
trial stage.2  Stem-cell therapy treatment for genetic 
disorders has large potential as a long term solution.  
Currently stem cell therapy is being looked into 
readily because it appears to be a possible cure for 
muscular dystrophy.
 Stem cell therapy is the use of stem cells to treat 
various diseases with no other known cure.  Stem cells 
can be acquired from various locations in the human 
body or generated in vitro.  Bone marrow has been 
used to treat cancer for quite some time, but the use 
of stem cells in genetic diseases is being continuously 
researched.  Stem cells are considered a possible cure-



Muscular Dystrophy: Stem Cell Therapy

Aisthesis      Volume 7,  201639

all because of the potential for stem cells to replace 
cells with malfunctioning proteins.  
 Stem cells have been used to treat diseases in the 
past, but the use of these various cells to treat muscular 
dystrophy is being heavily researched.  There is more 
than just one type of stem cell, so these various types 
are being researched to determine which cell has the 
greatest effect on muscular dystrophy.  Stem cells can 
be administered to muscles in different ways, and 
this is also being researched to see what methods are 
most effective.  Depending on the type of stem cell and 
how it is introduced to the muscles, the effectiveness 
can greatly vary and this is what is being investigated. 

Stem Cell Therapy in Muscular Dystrophy: Methods 
of Injection
 Early assessment with stem cells used mice 
to test the effectiveness of different injection 
methods.  The mice used have a genetic disease 
similar to Duchenne muscular dystrophy found in 
humans, and the mice are a referred to as mdx mice.5  
Experimentation with mdx mice focusing on stem cell 
injection was conducted by Gussoni et al.  Gussoni 
et al.’s experiment compared the different types of 
stem cell injections to see which method is most 
effective at delivering cells to the desired areas.5  The 
method of injection is a very critical portion to the 
treatment, because even if stem cells are found to be 
highly effective, they will have no effect in the body if 
the cells cannot reach the area of interest.  Gussoni et 
al. compared two different stem cell injections based 
on injection methods used to treat other diseases.
 In Gussoni et al.’s experiment, mice were injected 
with stem cells in two different ways: either directly into 
specific muscle areas of interest, or intravenously, 
similar to a bone marrow transplant for leukemia 
patients.5  The target areas for stem cells are the muscles 
where dystrophin is not functioning properly, so the 
method that more accurately reaches these areas is 
being tested. 
       Gussoni et al. found that directly injecting stem 
cells into the muscles ensures that the cells reach the 
area of interest.5  A downfall of this injection process 
is that it is costly because of the instruments and 
surgery time needed.5  Muscular dystrophy affects most 
muscles in the body, so stem cells have to be injected 
throughout the body.  Once the stem cells are injected, 
the cells are localized to the area of injection, so 

many injections are needed to cover the complete 
body.4 
       Intravenous treatment is an injection into the 
vascular system, the blood vessels.  This method is 
how leukemia is treated with bone marrow and is 
found to be very efficient.  Introducing stem cells 
intravenously involves injecting the stem cells into 
the blood stream and allowing them to move on 
their own to each area of the body.5  If the stem cells 
are small enough, they can diffuse from the blood 
into all muscle areas.  Such diffusion would require 
much fewer injections and materials, and it would be 
less painful for the patient in total.  This method of 
injection would be convenient, be cheaper, and put 
less stress on the patient.5  The success of the treatment 
lies completely on the ability of the stem cells to be 
able to move from the blood vessel walls into the 
muscle.  
       Gussoni et al.’s experiment shows that injection 
by both methods is very possible, with both methods 
involving the integration of stem cells into the 
muscles.  Intravenous treatment appears to be the 
most effective, but only if the stem cells can diffuse 
through the vessel wall.5   Gussoni et al. found that if the 
most effective stem cells cannot diffuse through the 
vessel walls, direct injection is effective but requires 
many injections to the muscles.
 Gussoni et al.’s experiment showed that stem cell 
therapy is highly probable as an effective treatment.  
The experiment they conducted also showed that 
stem cells do work in mdx mice to help restore 
function to dystrophin.5  The possibility that function 
was partially restored was a huge breakthrough since 
previous studies of directly injecting the dystrophin 
protein had not worked.5  There are many different 
types of stem cells, and testing was next conducted 
to see which cells resulted in the greatest increase in 
dystrophin function.

Stem Cell Therapy in Muscular Dystrophy: Types 
of Stem Cells
         The ability of muscle cells to partially regenerate 
led to the realization that there were stem cells that 
directly relate to the muscle, or stem cells that could 
be adapted to allow for increased muscle function.6  
There are several different cells that can perform 
these functions, and Price, Kuroda, and Rudnicki 
reviewed different types of stem cells that are being 



Muscular Dystrophy: Stem Cell Therapy

Aisthesis      Volume 7,  201640

tested and have the possibility of being used as a 
treatment for muscular dystrophy.6   The experiments 
that Price et al. reviewed were all conducted on mdx 
mice, same as in testing the injection methods.
       Price et al.’s analysis of previous experiments found 
that regeneration of muscles is led by muscle satellite 
cells, a muscle specific stem cell.  Muscle satellite 
cells recruit nonspecific cells to fuse and differentiate 
into the new muscle fibers, so muscle satellite cells 
facilitate the creation of new functioning fibres to 
replace the fibres damaged from malfunctioning 
dystrophin.6  In muscular dystrophy, muscle satellite 
cells cannot replace the cells with the malfunctioning 
dystrophin protein.  Price et al. found that these satellite 
cells are completely exhausted with their function 
depleted, so new fibres are not replacing the damaged 
fibres.5,6  Gussoni et al.’s experiment also found that 
stem cells were not maturing to functional muscle 
cells after replication, like the cells’ normal process 
for maturation, but instead remained stem cells.5,6  

Satellite cells were transplanted directly in order to 
replenish the depleted satellite cells and to function 
for the stem cells that were not differentiating to 
muscle cells.  Price et al. saw there were positive results 
of restoring dystrophin function three weeks after 
injection, a promising start to a possible long term 
treatment.6  
       In order for satellite cells to be used as treatment, 
the cells must be isolated from the body.   Isolation 
of these satellite cells is problematic because they are 
mainly found in core muscles like the diaphragm.6  

Isolating these cells from the diaphragm is difficult 
and would require surgery, and because cells are not 
able to be seen without a microscope, it would be 
difficult to extract the cells.  The possible use of muscle 
satellite cells is diminished by the difficulty in 
acquiring the cells for treatment.
       Previous success with muscle satellite cells had led 
to experimentation that involved generating a similar 
cell, but one that could be more easily acquired.  
Building on this research, Price et al. found that satellite 
cells could be generated in vitro, meaning the cells 
were grown in a lab, most likely in an isolated petri 
dish or test tube.6  Generating these cells in vitro is a 
much easier way of isolating this specific type of cell 
than extraction, and these generated cells are given 
the name primary myoblasts.  Primary myoblasts 
were given their own name because these cells may 

behave differently when generated in vitro compared 
to the muscle satellite cells isolated from the body.6  
Price et al. determined that myoblasts could be 
injected right into the muscle of concern, were easily 
cultivated, and showed success in increasing the 
dystrophin protein’s function.6  
       With high promise from these results in mice, Price 
et al. observed the effect of myoblasts on non-human 
primates to see if the myoblasts would be accepted by 
the body and what the immune response would be.6,7   
The myoblast were successfully integrated into the 
primates, but it was unclear whether the cells would 
provide any phenotypic change to dystrophin.6   The 
primate trial showed that it was very possible that 
myoblasts could be accepted by the human body 
as well, because of the similarity between the two.  
Human clinical trials with myoblast injections began 
in the 1990s, but data was originally inconclusive 
as it proved difficult with limited technology to 
determine if the dystrophin had been corrected.6  
Studies are still being conducted to determine the 
total effects of myoblast transplantation on the 
human body and dystrophin.  Even with the success 
of myoblasts, other stem cells are being researched to 
see if they have even better results.
       Price et al. discussed another set of stem cells 
in muscles, in addition to the satellite stem cells, 
called side population cells.  These cells can be found in 
both muscle and bone marrow, and they still possess 
myogenic potential when transplanted into the muscle.6  
Dyes are used to isolate the side populations.  These 
cells are not as difficult to isolate as are the satellite cells 
since side populations are found in more accessible 
areas.  The muscle side population cells regenerate 
muscle, but the regeneration is through a different 
path than the other stem cells in the muscle.6  One 
of the more promising contributions of the muscle 
side population cells is their ability to move from the 
blood to the muscle, meaning there is a possibility 
for the cells to be injected into the vascular system 
and reach many muscles throughout the body.6  This 
is the ideal method of injection that was discussed 
previously, so if the side populations function as 
predicted, they will be the ideal treatment.  The 
muscle side population cells’ regeneration abilities 
are not nearly as long term, as are the abilities muscle 
satellite cells.  Despite side populations’ ability to be 
injected intravenously, the cells do not last as long as 



Muscular Dystrophy: Stem Cell Therapy

Aisthesis      Volume 7,  201641

desired, so other stem cells were looked in to.6
       Another type of stem cell that Price et al. 
observed to be used as a treatment is bone marrow. 
Bone marrow was tested due to the bone marrow’s 
success in decreasing the effects of certain cancers.  
When bone marrow is injected into the blood, it 
differentiates into new blood cells, which is why it is 
used to treat leukemia.6  Price et al. found through 
experimentation with mdx mice that the stem cells 
in the bone marrow can differentiate into myogenic 
cells, meaning that bone marrow can be used in 
muscle repair.6  In the mdx mice, dystrophin was 
repaired, and it was found that the bone marrow 
cells stayed in the musculature longer than did any of 
the previous treatments while cells still maintained 
dystrophin expression.5,6   The process of the bone marrow 
converting from bone cells to muscle cell is still 
unknown.  Despite the mystery of the process, bone 
marrow still has many positive aspects to be used 
as a treatment.  One of the major positive aspects is 
that bone marrow is injected intravenously, the ideal 
injection method.  This type of stem cell changes from 
bone to muscle, and it is similar to embryonic stem 
cells in their ability to differentiate into a variety 
of cell types, and embryonic stem cells have been 
studied greatly in the past.
       Price et al. found that embryonic stem cells were 
originally thought to have the solution to genetic 
diseases.  The lack of breakthroughs in recent years 
in the use of embryonic stem cells has decreased 
research in this area.  These stem cells hold a lot of 
promise because they are the cells that all organs 
originate from, so there is no question of whether 
they can differentiate into the desired cell or not.6  
The use of embryonic stem cells to grow new muscles 
was first conducted approximately 20 years ago.5  
The efficiency of muscle growth by these cells has not 
been improved in recent years, so it is not often used 
as a viable transplantation option.  Embryonic stem 
cells do show promise in gene analysis, where specific 
genes can be targeted.  Genes of interest can more 
easily be isolated to see how their function relates 
to muscle acitivity.5  By studying embryonic cells in 
vitro, there is an increase in knowledge regarding the 
molecular process of muscle growth and formation.5  
The information found from the in vitro gene analysis 
is currently not being used clinically, and more 
studies are needed to be conducted before proved 

useful.  Currently embryonic stem cells are not used as 
a treatment, but there is still a great deal of potential 
that may arise with future technology and research.

Stem Cell Therapy: Health Concerns
 In stem cell therapy, some of the cells that may 
hold the most information are embryonic stem cells, 
cells that are the subject of great controversy.  The 
embryonic stem cells used in research are those 
that have been grown in vitro, meaning they were 
cultivated in a petri dish and never created inside 
a human being with the intent for life.  Others still 
believe that use of in vitro stem cells is unethical, and 
experiments can have difficulty being funded due to 
the controversy surrounding the subject.
 Besides ethical concerns with stem cell treatments, 
there are also health concerns.  The body’s immune 
response to stem cells is something that must also 
be considered during treatments.7  Anytime a foreign 
substance is injected into the body, the body’s 
immune response has to be closely monitored.   When 
stem cells were injected into mdx mice and humans, 
immunosuppression had to occur to allow the foreign 
stem cells to be accepted by the body and not 
destroyed.7  This means the immune system, in a 
sense, must be turned off to allow for treatment to 
take place.  The suppression of the immune system 
is why many people undergoing cancer treatments 
can become sick very easily, because other illnesses 
have a higher chance of infecting individuals when 
the individuals are being treated.  When a person’s 
immune system is suppressed, the microbes that 
are commonly destroyed by the immune system are 
allowed to thrive and can lead to severe illness.  The 
immunosuppression is required, because studies have 
shown that within an hour of injection, 90% of the 
injected myoblasts were removed by the immune 
response, meaning they would not reach the muscle 
to have a chance to affect dystrophin.7  
       Scientists have also considered the possibility that 
the immune response could be attacking the newly 
functioning dystrophin.  The new dystrophin from 
the injected stem cells is not a naturally functioning 
protein in the person’s body, so its function may 
be seen as a foreign threat.7  With clinical trials of 
several stem cells being tested, the immune response 
is a present concern for doctors.
 The immune system is the major concern, but the 



Muscular Dystrophy: Stem Cell Therapy

Aisthesis      Volume 7,  201642

differences in the subjects of the stem cell treatment 
have to be considered.  There are differences between 
muscular dystrophy in mice and humans.  The 
muscle in mice is more resilient, so the fibers can 
reform and the disease is less severe.5  Mice muscles 
and human muscles have different characteristics, 
and these differences must be known before testing 
can be done with human stem cells.5  The differences 
also mean that there is no definitive proof that these 
treatments will have any effect in humans.  Studying 
mice allowed for a great deal to be learned about 
stem cells and how they function in muscles, but 
clinical test on humans must proceed with caution 
because of possible unexpected side effects that may 
have not been seen in the mdx mice.

Conclusion
       Muscular dystrophy is a genetic disease that greatly 
decreases the quality of life for many individuals 
by decreasing muscle function.  There are many 
studies being conducted on the possible application 
of various stem cells.  Dystrophin is isolated as the 
protein responsible for the muscle malfunction in 
Duchene muscular dystrophy, the most common 
form of muscular dystrophy.  At this time, myoblasts 
are the type of cells that have had the most clinical 
trials, and show a great deal of promise.  Other 
cell types are currently being tested, with various 
clinical trials underway.  The clinical trials focus on 
the ability of the stem cell to increase dystrophin, as 
well as how easy it is to acquire the cells and how 
easy it is for them to be injected into the body.  With 
any type of medical treatment, there are several 
controversial aspects that present themselves as 
well.  These include ethical concerns that arise with 
generating cells in vitro and how the immune system 
will respond to new stem cells in the body. Despite 
concerns, research still holds promise with many 
stem cells being clinically tested, myoblasts being the 
most favored stem cells currently.  All of the different 
stem cells have certain characteristics that work as a 
possible treatment, and only after clinical trials will 
the most effective cell be found.

References
[1] Muscular Dystrophy Assoc. (2009) Facts About 
Duchenne & Becker Muscular Dystrophies.  Retrieved 
Sept. 3, 2015, from http://www.mda.org/sites/default/
files/publications/Facts_DMD-BMD_P-211_0.pdf 
[2] Nowak, K. J., & Davies, K. E. (2004). Duchenne 
muscular dystrophy and dystrophin: pathogenesis and 
opportunities for treatment. EMBO Reports, 5(9), 872–
876. http://doi.org/10.1038/sj.embor.7400221
[3] MedlinePlus. (2015, August 26). Muscular 
Dystrophy. Retrieved September 3, 2015, from  h t t p s : / /
www.nlm.nih.gov/medlineplus/musculardystrophy.
html 
[4] Thakur, S. (n.d.). The Dystrophin Protein: 
Structure, Function and Role of Post-Translational  
Modifications. Retrieved September 3, 2015, from  
http://www.academia.edu/5274274/The_Dystrophin_
Protein_Structure_Function_and_Role_of _ P o s t -
Translational_Modifications 
[5] Gussoni, E., Soneoka, Y., Strickland, C., Buzney, 
E., Khan, M., Flint, A., et al. . Mulligan, R. (1999).  
Dystrophin expression in the mdx mouse restored 
by stem cell transplantation. Nature 401 (6751): 390-
394.  Retrieved September 24, 2015.
[6] Price, F., Kuroda, K., & Rudnicki, M. (2007). Stem 
cell based therapies to treat muscular dystrophy.  
Biochimica Et Biophysica Acta (BBA) - Molecular 
Basis of Disease, 1772(2), 272-283. 
[7]  Maffioletti, S., Noviello, M., English, K., & 
Tedesco, F. (2014). Stem Cell Transplantation for 
Muscular Dystrophy: The Challenge of Immune 
Response. BioMed Research International, 2004, 1-12.


