One step closer to a viable cell replacement strategy for muscular dystrophy

Author: Angela C. H. McDonald, 06/07/12

Late in May, the Brampton Fire Department (just outside of Toronto) held a “boot drive” to raise money for Muscular Dystrophy.  My boyfriend who happens to be a firefighter tells me that boot drives are fairly common among Canadian fire departments.  In fact, they are often specifically supporting Muscular Dystrophy Canada.  At a boot drive, firefighters set up shop in community spaces and literally fill their boots with donations.

The fire departments have chosen a worthy cause to support as approximately 50,000 Canadians suffer from the disease. Muscular dystrophies are a group of neuromuscular disorders caused by genetic mutations resulting in progressive muscle weakness and muscle wasting.  Severity of symptoms, age of symptom onset, speed of progression and muscles affected can very between each form of muscular dystrophy.  These disorders may become severely debilitating or fatal over time as patients can lose the ability to walk, speak or even breath. Currently, there is no cure for muscular dystrophy.

Recently, an exciting report was published in Cell Stem Cell describing the generation of expandable muscle stem cells from human pluripotent stem cells.  These muscle stem cells were transplanted into a mouse model of muscular dystrophy, engrafting into leg muscle and significantly improving muscle function.

While muscle stem cell (known as satellite cells) replacement strategies in muscle wasting conditions have long been a desired treatment strategy, we have not had access to a sufficient number of muscle satellite cells for transplantation.  Enough satellite cells for transplantation cannot be obtained from a donor muscle without causing severe or permanent damage.  In early clinical trials, small numbers of satellite cells were obtained, expanded ex vivo and then transplanted into Duchenne’s muscular dystrophy patients (the most common form of muscular dystrophy).  However, no improvement was observed.  It is thought that ex vivo expansion changes functional properties of the satellite cells.

The current study provides a novel, renewable source of muscle satellite cells that could one day be used for transplantation into human patients.  To generate satellite cells, human pluripotent stem cells were first differentiated into mesoderm (the germ layer in which satellite cells are derived) and then the PAX7 gene was over-expressed.  The result: an expandable pool of satellite cells that are capable of differentiating into mature, multinucleated myotubes.

When these satellite cells were transplanted into muscular dystrophy mice, high levels of engraftment were observed and engrafted cells could be detected 11 months following transplantation.  Many transplanted cells had differentiated into mature myotubes but some did remain as satellite cells.  This is important because the replacement of satellite cells means that new myotubes can be formed over time.

How does PAX7 expression create expandable satellite cells?  The answer to this question can be answered, in part, by work from Michael Rudnicki and his group, who have been investigating how PAX7 works at the molecular level.  Their work recently published  in Developmental Cell describes the ability of PAX7 to bind directly do DNA regulatory regions (regions controlling gene expression) of genes involved in proliferation (cell expansion) and inhibition of muscle differentiation (important for maintaining satellite cell self-renewal).  Rudnicki’s work provides important insight into the function of PAX7, which is distinct from other genes involved in muscle maintenance.

PAX7-induced human satellite cells as a renewable cell source is exciting but far from the clinic.  But this work provides researchers a solid basis for optimization of a viable source of muscle satellite cells that could one day be used for cell transplantation therapies.

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Angela C. H. McDonald

Angela C. H. McDonald

PhD candidate at Hospital for Sick Children
Angela is a PhD student in the Stem Cell and Developmental Biology program at the Hospital for Sick Children in Toronto. She is currently utilizing pluripotent stem cells to understand the genetic regulation of endoderm development. As an avid supporter of public science education, she co-founded the high school outreach initiative StemCellTalks sits on numerous public education committees including the International Society for Stem Cell Research Public Education Committee and the Stem Cell Network Public Outreach Committee.
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One Response

  1. Sonsu kim says:

    WMDROC reveal “Why Scientists still can not develop a muscular dystrophy cure medicines?”

    First of all, I want to say that it is very regrettable for the patients or their family of Muscular Dystrophy who have awaiting the development of muscular dystrophy therapeutics with drugs and /or as planting stem cells or adults cells, chromosomal or genetic manipulation in the field of modern science. But I think that it is more important than what if they are so awakening to change the directions of the treatment that find a new way to live and to save their lives, as I reveal the truth of the current situations and inform my sincere.

    First before saying, I clarify my claim or my story to be commence, apart with any scientific logic for MD treatment of modern scientists and /or researchers, based on the practical experience of treatment in accordance with my way.

    I have ever received an offer its treatment drug development from one of famous pharmaceutical manufacturers in Korea, but I have refused it flatly, because for me to cure these muscular dystrophy is belong to use the principle of effects of physical changes that can physically adjust the energy flowing in the human body but not to attempt principles to switch to chemical changes in the physical act.

    It may be very excuse but I want to ask one thing to modern scientists and researchers dealing with this disease. How could they made imagine that these disease can be cured with the chemical medicines or injections? How could they dreamed that these disease can be treated as planting stem cells or adult cells or genetic manipulations?

    The human body is only one of the byproduct of natural in the universe.

    Although genetic disorders or some chromosomal defects might be possessed by these disease patients, but these kinds of reasons can not be the whole causes for MD onset. Do you know why? For the most of DMD patients, even they may having some disability for their walking, are normally growing up in childhood from the birth. But whenever the time is coming, their growing is suddenly stopped and all muscles on the body beginning loss, all tendons on body shrink, spine vent as if a bow or a snake moving “S” type.

    If the causes of generating DMD in these kind of patients simply belong to genetic or chromosomal defects or disorders in accordance with modern medical scientist’s talking about. How could they grow up in childhood as well as other children from the birth? And why suddenly stopped their growing up as the onset when they reached a some moment? Why they began muscles loss, tendons shrink, spine vending from this moment?

    For making actual MD cure, it is not much more important to join issue with genetic disorders or chromosomal defects as the causes of MD generation. But it is very important to choose one thing between actual cure experience and theoretical treatment.

    Let me talking about actual cure.
    In the actual cure for MD, there is no way to reach it except with a compendium to make all of internal organs, I mean lungs, heart, livers, gal bladder, spleen, stomach, kidney, large intestine and small intestine, bladder in abdominal cavity increasing up in their every each functions, volumes or capacities for getting more breathing, more blood circulations, more food in-taking to product more nutrients and more supplying on the every each parts of body demand. Then you will know our intake food becomes a superior medicine for MD treatment.

    Can you imagine for you that you can make these cure medicines of such characteristics as the chemical compound, no matter how mixed the various ingredients complicates, which all of functions, capacities of internal organs can be upgraded more or less at mean time and together?

    Can you expect to MD patients that it will be possible all of functions, volumes of internal organs can be increasing up at mean time and together as well as weeds in a field and the trees in the forest disseminate, if you planted stem cell or adults cell into their body, or if you manipulated the genes of MD patients?

    Past time before western medicine coming in the East, oriental medicines have been classified into three categories. there were about the kinds of senior class, intermediate class, junior class. The superlative of medicines was to do immortality, intermediate of medicines to ensure the health, the lower of medicines to cure illness.

    In the history of the past, there were many emperors in China. They died early on average age than the general old population. The causes of death were almost poisoning accident rather than ruin by war or by assassination of political enemies. Greatest aspirations of the emperors who died in these poisoning accident were their own immoralities than ideal operating in their empires. they were to create medicines for immortality and taking it for a long-term, but the drug ingredient of the long-term doses was rather poisonous and also increasingly accumulate in the human body caused their deaths.

    We often cited and used for our life the words of ” Birth, Old, Illness, Death. ”
    Exactly to say, the word of “Birth” can means born but it also belong to growth from born if widely to say, because it belongs to also a new birth that new cells arise with existing cell proliferation. We should be considered as a course of birth until the moment of growth stops.

    Meaning of the word “Grow old” is stopped growing and degeneration begins. Strictly speaking, it is not the maintenance of the current state. There should not be any difference that to make the development medicine for maintain current state on the body of MD patient compared with the medicines what successive Chinese emperors had so crave for immortality.

    Which researchers, which scientists, and which medical doctors, even which any people of us, who can and how can make such medicines enable to maintain the current state of the body in now or next year, even after ten years? Remedy for stopping the ongoing muscular dystrophy should be developed equivalent efficacy above described immortality of successive Chinese emperors. The drugs what can be to stopped progress to muscular dystrophy so, its effects must possesses even in the general public by taking it. it should continue to keep the teenager’s youth if teens are taking it, thirty years old youth if thirty years old taking it.

    Furthermore, in order to reverse or cure the symptoms of progressive muscular dystrophy, we should be developed a drug of the effect which will be re-growth for the body stop growing and increasingly degenerate.

    The characteristics of the drug, although anyone of mature or old age who growth has already gone away, must all human tissues and cells to be so activated and to be so lived again that the state of the body have to go back to the state of growing body. In other words, no matter how any one having old the body, if they continue to take this drugs for a period of time, they must go back to the days when the growth of the body again, and have to become hard muscles, and smooth tendons, and the skin revive to enrich, hair re-darkened, and wrinkles is supposed to be dismissed. The drug will be undying to the people who has a lot of money even after a thousand years, a million years if they buy it for taking continuously. Therefore, the development of such cure drugs embrace these challenges in this era.

    All the features of our body and its shape is derived from the internal organs. Our body’s internal organs are same as if the nucleus of atoms. As long as special incident is not happened, it is whole role for Internal organs that food, water, air, etc what we intake, have been so changed benefits on our bodies that faithfully send every each part of body in accordance with a necessary. Who can make us, human grow? Parents, nature, food is not to be this role but these are just only belong to assistance or help things.Those who direct work to grow our body so, are because of the invisible labor of internal organs in the our body.We have to know how to thank you for the our internal organs, rather than God who do not know his existence even if he may be or not may be or the historical Buddha who died thousands years ago, that grow and maintain this our body.

    The idea of modern scientists and researchers to find MD treatment, as plating stem cells or adult cells, or any genetic manipulation against Muscular Dystrophy which causes by stop and degeneration of internal organs growth, is really nonsense. Their performance, compared to the costs, times, efforts and investments, is nothing but only freshly bubble of water. Now MD patient is dying because his own stem cells or adult cells can not be properly nourish in his body.

    Is it possible for MD patients to make a healthy body if planted in the body of the patient the cells which have cultured or brought from elsewhere, the patients internal organs can supply nutrients properly given, proliferation grows, spread out all over the body? Would you expect to be proliferate and spread to others in a circumstance that you can not maintain yours?

    If crops already planted are dying.
    Give them enough water and a manure to resurrect.
    It is a job of the farmers that give crops water and a manure.

    If trees in garden are dying in dry weather.
    Give them enough water to resurrect.
    It is a job of the garden owner that give trees water.

    If cells of body is dying because owing to shortage of nutrient supply,
    Give them enough nutrient supply.
    It is a job of internal organs in the body.

    For these crops or trees, without thinking need to water and fertilize, some one is going to plant the seeds of new trees or crops unconditional. For the problem of existing own cells dying with the shortage of nutrient supply to the human body, somehow they did not thought to be done the nutrient supply for revival but are thinking to plant new cells with only hope that it will be grows and spread well MD patient body. This, trying to get the effect of newly planted stem cells or adult cells, is a goal of cure for MD that most of modern scientists and researchers were craving so.The existing cells in the body of the patient are dying now because nutrients are not supplied by internal organs of these patients. Is it possible to expect that these internal organs may be able to nutrition supply for the newly transplanted cells? Is it possible for newly transplanted cells to grow and to be proliferation of new cells without nutrition supply by the internal organs?

    In order to grow or maintain the human body, the mission of creation, transportation, dispersion for necessary nutrients is not to interfere directly as human judgment and commitment, but should be carried out entirely by internal organs. We should not miss seeing the inside of this disease as temptation being to action phenomena visible. Leave the treatment of these diseases in the internal organs, we, should take good care of the internal organs of our body.

    The differences of patient feature before and after adjusting whole internal organs.

    If internal organs stop their own growing and then very rapidly so shrink that becoming supply of nutrients
    reduced, the body is collapsed, muscle is exhausted, tendons shrunk, skeleton is twisted even, this situation is the disease name of MD.

    As a one of human being who living at same time in same world, I’m really worrying about this situation which the scientists and researchers have lost the direction of development these kind of disease treatment under the light of modern science and just hang around outside of treatment method.

    What is the cure of MD? there is no way except to prevent the degeneration of the internal organs and only revert back to the state they were in before. If I can do that because I know it already. You can do that if you know it now. We, every one of us, human will know it if they learn it in future.

    Written by founder of , Sonsu Kim

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