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Thread: FAO Dr. McIntire - interesting muscle study results

  1. #1
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    FAO Dr. McIntire - interesting muscle study results

    Maybe this can be used eventually to "sup-up" muscles to fight curves.

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    Rebuilding Muscle

    Lisa D. Chong

    Skeletal muscle injury can be debilitating and potentially lethal. Factors released by the damaged muscle can stimulate local skeletal muscle stem cells (satellite cells) to become motile, proliferate, and differentiate into replenishing myofibers. Stark et al. now suggest that even satellite cells distant from a site of injury could be recruited to help. The authors found that satellite cell motility was controlled by cell surface proteins called Ephrins that are expressed by healthy and regenerating muscle cells. Ephrins and their Eph receptors function as a guidance system in a variety of developmental processes. Ephrins elicited a repulsive signal that caused satellite cells to alter their migratory course. Mouse satellite cells grafted into either the developing hindbrain or limb bud of quail embryos respected Ephrin-defined boundaries as they migrated in vivo. The authors propose that Eph-Ephrin interactions may modulate satellite cell migration and patterning during muscle fiber development.

    Page et al. have used microthreads of fibrin to restore muscle function in mice with substantial leg muscle injury. When placed into the damaged area, the microthread scaffolds, seeded with adult human muscle cells that were coaxed into a stem cell-like state, restored healthy muscle fibers. Suprisingly, most of the new muscle was generated from recruited mouse satellite cells. Together, these studies point to potential therapies for treating major muscle injuries.

    Development 138, 5279 (2011); Tissue Eng. Part A 17, 2629 (2011).
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

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    BTW, that blurb was published in Science.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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    The research around muscle regeneration after severe injury is pretty amazing stuff. I'd love to collaborate with a lab that grows this stuff from satellite cells and then I could test the functionality of the muscle. A great friend of mine does stem cell differentiation on cardiac muscle cells. She spends so much time trying to get them to differentiate and then start beating that she has no idea how well it actually functions as a real cardiac cell. But that's how research goes. One expert does one thing and the next expert does the next and so on. We all stand on the shoulders of giants (love that from Google Scholar although I'm sure someone else said it first). Another lab down the hall does satellite cell work. He helped me separate out some muscle fibers a few months ago. So amazing. I'm relatively new to basic science work so my head explodes routinely when I see a new technique. :> Especially when it deals with muscle.

    At any rate, the first study about eph/ephrin is interesting from a developmental point of view. In the context of AIS, I'd wonder how this might be involved during puberty and spinal muscle development or a lack thereof, or if this is just during fetal development. Eph/ephrin seems to act a directional signal either attracting or repelling satellite cells to different areas. On a side note, I read the intro to that paper and read that in their earlier studies they showed a satellite cell can migrate almost 2.5 cm in 24 hours. That's just crazy to think about. So you get an injury to the muscle and immediately they start flocking to the injury site.

    The second article is mostly about severe trauma with great losses of muscle tissue like in battle wounds or auto-accidents. (This is becoming a 'holy grail' of sorts in muscle research right now, i.e. making large muscle tissue implants for use after severe trauma.) I would continue to operate under the assumption that AIS spinal muscles are otherwise normal and they have just atrophied for some reason. Thus, providing a stimulus like this, probably wouldn't be necessary. If, however, it could be shown that AIS muscle is not otherwise healthy, then some form of correction might be possible. But again, if there is something 'wrong' with AIS muscle, making this from their own stem cells would potentially just give them the same muscle that is prone to the same genetic problems.

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    I was able to glance at that second article as well. Really amazing in vivo results.

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    If the AIS muscles aren't healthy, couldn't they just biopsy them and find out? And by healthy, do you mean the actual structure of the muscle fiber itself, or the nerve pathways to the muscle? Either way, one would think that the "normalcy" of a muscle could be determined with microscopy. Would it be too costly to do electron microscopy on a large number of individuals? It would seem rather easy to get the samples from people already having the surgery. Anyway, that seems like a question that should be reletively easy to find out, unless I'm missing something.

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    Quote Originally Posted by rohrer01 View Post
    If the AIS muscles aren't healthy, couldn't they just biopsy them and find out? And by healthy, do you mean the actual structure of the muscle fiber itself, or the nerve pathways to the muscle? Either way, one would think that the "normalcy" of a muscle could be determined with microscopy. Would it be too costly to do electron microscopy on a large number of individuals? It would seem rather easy to get the samples from people already having the surgery. Anyway, that seems like a question that should be reletively easy to find out, unless I'm missing something.
    Yes, we could do a biopsy of the muscles and test them. But would the dysfunction be systemic or would it be local to the spine or even more local to the area of the curve, e.g. the apex? There have been differences found between AIS and healthy controls. But I think they've all been based on the paraspinals taken during either a surgery for AIS or during some other non-spine, but thoracic, related surgery (controls). I don't know that Ive read any study showing a systemic muscle dysfunction in AIS (although I don't know this for a fact. I'm remembering a few studies on melatonin receptors or osteopontin or calmodulin... something.. Again, I don't know if these were taken from extremity muscles or from the spine.) The size of the curve would also confuse the findings. So my general question about the 'health' of the AIS muscles relates to whether any present dysfunction is systemic, and therefore would most likely be detectable in any muscle collected, i.e. a much easier study, or local to the paraspinal muscles, and would be nearly impossible to test.

    Re: "healthy muscle". Any of the things you mentioned could be possible sites for dysfunction. But in general I would think about the basic structure, function and metabolism of the muscle. Does it look the same? Does it contract the same? Does it signal appropriately under various contractile, nutritional and hormonal situations? There are a number of ways to measure this but I can't think of any specific AIS 'fact' that would justify looking at this, i.e. nothing a grant review board would potentially fund. This is ultimately why I think it's a safe bet right now to assume that any muscle involvement with AIS is secondary. Or at least it's safe to assume that AIS muscle is just as healthy as 'normal' muscle.

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    Quote Originally Posted by Kevin_Mc View Post
    This is ultimately why I think it's a safe bet right now to assume that any muscle involvement with AIS is secondary. Or at least it's safe to assume that AIS muscle is just as healthy as 'normal' muscle.
    Yes but if the muscles could be manipulated such that they would work like a hard brace then that would solve the compliance issue over night. That was my thought.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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    Still thinking about muscle structure/function here. Why would it not be feasable to biopsy the paraspinals and say a quadricep (for instance, something non-spinal or thoracic) during the same surgery? This would solve the problem of whether it is systemic or not. Yes, I've read some of the stuff Dingo pulled up on Melatonin signaling pathways and Osteopontin, so those research avenues are already "taken" per se. But I don't see anything unreasonable about studying the muscles of AIS patients. For structural purposes at least, you could get your controls from cadavers since obviously "healthy" individuals wouldn't be willing to be biopsied, nor would it be ethical. If the muscle has to be fresh, most people that donate themselves to science say so ahead of time and it would be possible to contract with a few hospitals that deal with this sort of thing to get the biopsies before embalming. I can't see the unreasonableness of a study on this subject if there aren't any, especially if you could relate it to the genetics, since that is the hot topic. I'm sure you could figure that out. I'm sure I'm oversimplifying things, but you get my meaning, I hope. The hard part, as you know, is putting together a grant proposal. But clever minds come up with clever ways to relate things. Just a thought, since this seems to be uncharted territory. It seems a shame not to look in this direction, especially if it might be somewhat "easy" to do the actual study stuff. It's just getting past the grant and through all the red tape.

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    Quote Originally Posted by rohrer01 View Post
    Still thinking about muscle structure/function here. Why would it not be feasable to biopsy the paraspinals and say a quadricep (for instance, something non-spinal or thoracic) during the same surgery? This would solve the problem of whether it is systemic or not. Yes, I've read some of the stuff Dingo pulled up on Melatonin signaling pathways and Osteopontin, so those research avenues are already "taken" per se. But I don't see anything unreasonable about studying the muscles of AIS patients. For structural purposes at least, you could get your controls from cadavers since obviously "healthy" individuals wouldn't be willing to be biopsied, nor would it be ethical. If the muscle has to be fresh, most people that donate themselves to science say so ahead of time and it would be possible to contract with a few hospitals that deal with this sort of thing to get the biopsies before embalming. I can't see the unreasonableness of a study on this subject if there aren't any, especially if you could relate it to the genetics, since that is the hot topic. I'm sure you could figure that out. I'm sure I'm oversimplifying things, but you get my meaning, I hope. The hard part, as you know, is putting together a grant proposal. But clever minds come up with clever ways to relate things. Just a thought, since this seems to be uncharted territory. It seems a shame not to look in this direction, especially if it might be somewhat "easy" to do the actual study stuff. It's just getting past the grant and through all the red tape.

    It's pretty simple to do a leg muscle biopsy on awake subjects. There are studies on it all the time. In fact, the first study I started working on out here, I had to arrange muscle biopsies for our subjects. Although it might be difficult with adolescents. Or rather, difficult to get them to agree. Probably even difficult to get that through a review board as well. At any rate, the point is that the muscle has to be fresh. Once the muscle goes without oxygen for ~3-5 minutes things start to degrade rapidly. So you have to harvest the muscle and then quickly freeze, incubate, or 'fix' the tissue in some way.

    After thinking about it some more, I can see a couple of possibilities. I'd of course love to do some studies on AIS muscle. But again, it's the funding. I wonder if the Natl. Science Found. would fund something. They are more prone to funding exploratory studies.

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    I definitely wouldn't give up on the idea. This is YOUR thing and uncharted territory! As you know, there are many places to get grant money from, and if you are clever enough, which I believe you are, you can make your study relevent to the already funded studies but with a big NEW twist that is a necessary direction to follow. You might really be on to something here. If nothing pans out, then you would be able to rule that out as a possibility. It's a win, win situation, as ruling things out is just as important as finding things. Keep wracking that brain of yours!

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    Quote Originally Posted by Kevin_Mc View Post
    . At any rate, the point is that the muscle has to be fresh. Once the muscle goes without oxygen for ~3-5 minutes things start to degrade rapidly. So you have to harvest the muscle and then quickly freeze, incubate, or 'fix' the tissue in some way.
    They keep donors "alive" so to speak until the families are ready to pull the plug. You could get your biopsies then. You would have to work out the detail and the ethics with the hospitals. I know it's kind of a greusome subject, but unfortunately a necessary one in medicine.

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    Quote Originally Posted by rohrer01 View Post
    They keep donors "alive" so to speak until the families are ready to pull the plug. You could get your biopsies then. You would have to work out the detail and the ethics with the hospitals. I know it's kind of a greusome subject, but unfortunately a necessary one in medicine.
    Honestly, I'd rather try my luck with review board approval getting adolescent subjects. It's really nothing more than some topical numbing, which burns a bit. But then the rest is painless although does feel a bit weird. Then a bit bruised and sore for a day or two. After that no big deal. They do repeated, like 5 or 6, biopsies on college students all the time during feeding and exercise studies. E.g. Take a baseline biopsy, tape it closed, workout hard with your legs, take a biopsy and tape it closed, eat a nutritional supplement, then 30, 60, 120, 240 minutes later take a biopsy and tape it closed. All of that in one leg although they'll probably make 2 or 3 incisions. Combine this with have an arterial and venous leg catheter for blood samples as well. Crazy. But really interesting data that comes out. Gotta love college kids. :>

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    I was thinking in terms of the paraspinal muscles. If you can get them from live willing subjects, that would be best. I most certainly agree. It would save a LOT of red tape and be much better quality. I was just under the impression for some reason that you wouldn't be able to get them. I don't know why I thought that. I'm sure healthy adolescents would be hard if not impossible to get samples from. Yes, your way is best. I totally agree. It's just my ignorance of the field.

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    I think this is good research, but I canít see how it can be applied in a really useful manner for scoliosis.
    To me it just seems like the bodyís normal mechanism of healing itself from injury.
    I believe the same as with Dr McIntyre (hope I spelled your name correctly)
    QUOTE >>I would continue to operate under the assumption that AIS spinal muscles are otherwise normal and they have just atrophied for some reason.<<

    But I also would not be surprised if there is some form of damage to the muscle structure from overstretching. But the problem is that I think this would relate to progression itself Ė not necessarily a cause factor.
    If you do a study where you only take samples from patients at the point of surgery, and it shows there is damage to muscle, the only useful question is at what point does this damage occur? And in order to find that out you would also need to take samples from patients who are not yet at the point of requiring surgery. You need a control group of samples from AIS patients prior to spinal rotation to find out whether the damage is a result of progression (secondary) or some type of cause factor in itself (primary).
    All learning is useful, by learning what it isn't you get closer to finding out what it is.
    I just don't think they are going to find anything wrong as a cause factor here.
    - Scott

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    Quote Originally Posted by Kevin_Mc View Post
    Honestly, I'd rather try my luck with review board approval getting adolescent subjects. It's really nothing more than some topical numbing, which burns a bit. But then the rest is painless although does feel a bit weird. Then a bit bruised and sore for a day or two. After that no big deal. They do repeated, like 5 or 6, biopsies on college students all the time during feeding and exercise studies. E.g. Take a baseline biopsy, tape it closed, workout hard with your legs, take a biopsy and tape it closed, eat a nutritional supplement, then 30, 60, 120, 240 minutes later take a biopsy and tape it closed. All of that in one leg although they'll probably make 2 or 3 incisions. Combine this with have an arterial and venous leg catheter for blood samples as well. Crazy. But really interesting data that comes out. Gotta love college kids. :>
    Yes, I know someone who signed up to be a "paid" guinea pig for a nerve conduction study. They placed the probe into his tongue from the outside under his jaw! It is amazing the things people will put themselves through. Even more amazing are some of the horrid things they do to test people for disorders and then charge them tons of money for the test! It happens every day.

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