Thread: ChinaSCINet Update

  1. #1471
    Paolo,

    The myelotomy in Kunming is done from the side, usually at the dorsal root entry zone to keep from cutting through any of the long tracts. Most myelotomies are done at the midline, which cuts through the posterior column tracts for the legs. When the myelotomy is done during the first week or two after the injury, necrotic tissue is under pressure and comes out of the opening. This leaves a cavity in which scaffolding can be placed. Note that this is only possible during the first 2 weeks after injury. In the chronically injured spinal cord, the necrotic tissue has already consolidated and there may be axons crossing the injury site. In fact, Carlos Lima and his colleagues use to cut a chunk of spinal cord out of the injury site, saying that they are removing "scar". However, he showed picture of histology of the removed pieces of cord and there were axons running through them. That is one of the reasons why I think that it is not a good idea to remove chunks of spinal cord out and why I think very little of the cutting out "scar" idea. I don't think that it should be done on chronically injured spinal cords.

    Wise.

    Quote Originally Posted by paolocipolla View Post
    Wise,

    about point 1, you have posted many times about doing a mielotomy (which you say it improves outcomes) which require cutting the spinal cord.
    How do you do that without causing more damage and more scarring?
    I think the same procedure might be used to insert a solid scaffold in the spinal cord, does that make sense?
    BTW you suggested me this solution using solid scaffolds last time we met in Italy.

    About point 2 would you have a look to this study?
    http://pubs.acs.org/action/doSearch?...ation=40025957

    It seems that axons have crossed the scaffold and functional recovery has been seen and documented by electrophisiology.
    While I agree that it is not something ready for clinical trials tomorrow (but maybe sooner than Cethrin and Muse cells) I would look into it (if you haven't yet) also because it is something done on animals one month after SCI, which should be close to chronic, while Cethrin and Muse cells have been tested just on acute that I know.

    About your point 3, what about people with a very severe SCI if not anatomically complete SCI, how do you bridge the gap in these people? Maybe a solid scaffold could help? Or a peripheral nerve bridge may work better?

    One more question, InVivo is investing a lot in biomaterials and planning clinical trials, do you thing it is built just around "hot air"? .. and you know I am not super excited about InVivo, but I would think they should have something.

    Paolo

  2. #1472
    Quote Originally Posted by td_trust View Post
    hello everybody,
    has anybody heard of www.sinostemcells.com ? or is it a scam too?
    they say they are the only hospital that has CT-guided intraspinal stem cell transplant. does anyone know if thats something new?

    Dr.wise do you know anything about sinostemcell and their procedure?

    thank you
    This group is offering unproven mesenchymal stem cell therapies for spinal cord injury and charging for the therapies. They should not be doing this. If they are doing a clinical trial, I would be applauding but they are not. Actually, there are several groups in China offering this therapy and charging for the therapy. I would wait until there is convincing clinical trial evidence that this therapy is beneficial.

    Beware of any place telling you that they have an effective cell transplant therapy and wanting to charge you money for the therapy. No cell transplant therapy has been shown to have beneficial effects or safe for chronic human spinal cord injury. So, if any place is telling you that they have an effective cell transplant therapy for spinal cord injury, please avoid them. If this were a legitimate clinical trial, they would not charge you for the therapy and they would post the trial on www.clinicaltrials.gov or similar trial website.

    Regarding CT-guided cell transplants, we decided not to use this approach in ChinaSCINet because CT cannot show the presence of blood vessels. They are inserting the needle into the spinal cord without knowing that the needles may be penetrating some blood vessel and causing a catastrohic hemorrhage that may further damage the spinal cord. It is one of the reasons why the investigators of ChinaSCINet chose to expose the spinal cord and inject the cells under direct visual inspection of the spinal cord, to avoid any possibility of causing a hemorrhage.

    Wise.

  3. #1473
    Senior Member Moe's Avatar
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    Will see how far ChinaSCINet will go. So far good news. By the end of phase III human trials, the others are still playing with rats...

    Back to ChinaSCINet topic please...
    "Talk without the support of action means nothing..."
    ― DaShanne Stokes

    ***Unite(D) to Fight Paralyses***

  4. #1474
    I moved some of the discussion concerning scar tissue formation and discussion with Jerry Silver to its own thread:

    http://sci.rutgers.edu/forum/showthread.php?t=211255

  5. #1475
    Hey guys new here wanted to know how many potential cures for sci
    are in stage 3 clinical trials

  6. #1476
    Super Moderator Sue Pendleton's Avatar
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    Quote Originally Posted by Wise Young View Post
    Regarding CT-guided cell transplants, we decided not to use this approach in ChinaSCINet because CT cannot show the presence of blood vessels. They are inserting the needle into the spinal cord without knowing that the needles may be penetrating some blood vessel and causing a catastrohic hemorrhage that may further damage the spinal cord. It is one of the reasons why the investigators of ChinaSCINet chose to expose the spinal cord and inject the cells under direct visual inspection of the spinal cord, to avoid any possibility of causing a hemorrhage.

    Wise.
    Wise, You mean that it's not possible to do CT guided cell transplants because CT requires the person to be in the imaging equipment while the operation is ongoing? CT is the way anuerysms are monitored in my experience.
    Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

    Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

  7. #1477
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    Quote Originally Posted by Wise Young View Post
    Paolo,

    The myelotomy in Kunming is done from the side, usually at the dorsal root entry zone to keep from cutting through any of the long tracts. Most myelotomies are done at the midline, which cuts through the posterior column tracts for the legs. When the myelotomy is done during the first week or two after the injury, necrotic tissue is under pressure and comes out of the opening. This leaves a cavity in which scaffolding can be placed. Note that this is only possible during the first 2 weeks after injury. In the chronically injured spinal cord, the necrotic tissue has already consolidated and there may be axons crossing the injury site. In fact, Carlos Lima and his colleagues use to cut a chunk of spinal cord out of the injury site, saying that they are removing "scar". However, he showed picture of histology of the removed pieces of cord and there were axons running through them. That is one of the reasons why I think that it is not a good idea to remove chunks of spinal cord out and why I think very little of the cutting out "scar" idea. I don't think that it should be done on chronically injured spinal cords.

    Wise.
    I understand your reason for not cutting the scar tissue out.

    But is there any possiability of cutting slits into the scar tissue area and bridging the cord by that means or type of catalyst that might be able sofen for a better word the scare tussiue to allow better bridging or growth to occur.

    Didn't the SCS work on this problem at one stage?

    and when if some idea will both stage 3 and 4 be started and completed?

  8. #1478
    Quote Originally Posted by Leif View Post
    I would strongly support to not be posting the China data on CC until it is published in a journal. By that one will avoid the constant negative whining from non-productive people like Paolo.
    Leif,

    this is what I would do if the data I have indicate that the therapy does not work.

    More in details... I would spend a year or so trying to get the data publisched in journals that likely would refuse the publication to gain time.
    In the meantime I would do 10 more patients making sure they all get valid DTIs and electrophysiology exams (I would try also to include ASIA B and C) to make sure the therapy really does not work before giving up.

    In parallel I would get another therapy ready for clinical trials to be announced the same day I will have to say UCB cells don't work.
    That would mitigate the disappointment of the supporters.

    Of course here above I am just anticipating the worst case scenario, if UCB cells will show some efficacy all will be easier.

    Paolo
    Last edited by paolocipolla; 12-30-2012 at 08:57 PM.
    In God we trust; all others bring data. - Edwards Deming

  9. #1479
    Quote:
    Originally Posted by paolocipolla
    Wise,

    about point 1, you have posted many times about doing a mielotomy (which you say it improves outcomes) which require cutting the spinal cord.
    How do you do that without causing more damage and more scarring?
    I think the same procedure might be used to insert a solid scaffold in the spinal cord, does that make sense?
    BTW you suggested me this solution using solid scaffolds last time we met in Italy.

    About point 2 would you have a look to this study?
    http://pubs.acs.org/action/doSearch?...ation=40025957

    It seems that axons have crossed the scaffold and functional recovery has been seen and documented by electrophisiology.
    While I agree that it is not something ready for clinical trials tomorrow (but maybe sooner than Cethrin and Muse cells) I would look into it (if you haven't yet) also because it is something done on animals one month after SCI, which should be close to chronic, while Cethrin and Muse cells have been tested just on acute that I know.

    About your point 3, what about people with a very severe SCI if not anatomically complete SCI, how do you bridge the gap in these people? Maybe a solid scaffold could help? Or a peripheral nerve bridge may work better?

    One more question, InVivo is investing a lot in biomaterials and planning clinical trials, do you thing it is built just around "hot air"? .. and you know I am not super excited about InVivo, but I would think they should have something.

    Paolo


    Quote Originally Posted by Wise Young View Post
    Paolo,

    The myelotomy in Kunming is done from the side, usually at the dorsal root entry zone to keep from cutting through any of the long tracts. Most myelotomies are done at the midline, which cuts through the posterior column tracts for the legs. When the myelotomy is done during the first week or two after the injury, necrotic tissue is under pressure and comes out of the opening. This leaves a cavity in which scaffolding can be placed. Note that this is only possible during the first 2 weeks after injury. In the chronically injured spinal cord, the necrotic tissue has already consolidated and there may be axons crossing the injury site. In fact, Carlos Lima and his colleagues use to cut a chunk of spinal cord out of the injury site, saying that they are removing "scar". However, he showed picture of histology of the removed pieces of cord and there were axons running through them. That is one of the reasons why I think that it is not a good idea to remove chunks of spinal cord out and why I think very little of the cutting out "scar" idea. I don't think that it should be done on chronically injured spinal cords.

    Wise.
    Wise,

    if I understand correctly what you say the myelotomy does some damage, but the benefits of getting the necrotic material out surpass the negative effects of cutting the spinal cord as necessary.

    As I understand in real life probably more than 50% of traumatic SCI are much worse then the tipical contusion injury that is done in a lab on an animal. In fact penetrating bones in the spinal cord are not uncommon, that would cause signifinìcant fibrotic scar and not just gliosis, long gaps and sometimes even complete transactions of the spinal cord.

    What would be your approach in these cases?

    Sometimes I have had the impression that you consider just the kind of SCIs for which you believe UCB cells may do something and leave all the others behind, in fact, for example you have answered just partially to my questions which I think are of general interest. Hope you don't mind me beeing straightforward.

    Paolo
    In God we trust; all others bring data. - Edwards Deming

  10. #1480
    Quote Originally Posted by paolocipolla

    Wise,

    if I understand correctly what you say the myelotomy does some damage, but the benefits of getting the necrotic material out surpass the negative effects of cutting the spinal cord as necessary.

    As I understand in real life probably more than 50% of traumatic SCI are much worse then the tipical contusion injury that is done in a lab on an animal. In fact penetrating bones in the spinal cord are not uncommon, that would cause signifinìcant fibrotic scar and not just gliosis, long gaps and sometimes even complete transactions of the spinal cord.

    What would be your approach in these cases?

    Sometimes I have had the impression that you consider just the kind of SCIs for which you believe UCB cells may do something and leave all the others behind, in fact, for example you have answered just partially to my questions which I think are of general interest. Hope you don't mind me beeing straightforward.

    Paolo
    Paolo,

    Yes, cutting into the spinal cord will damage some tissue. In the early stages, a contused spinal cord is filled with dead tissue that is under pressure. The pressure results with the breakdown of the blood brain barrier and swelling of cells at the injury site. If you cut the spinal cord too early after injury, the spinal cord will "mushroom" out of the opening and the results may even be worse. Reginald Allen in 1911 and 1914 reported that a myelotomy and removal of necrotic tissues from a contused cord will restore function in dogs. Several attempts were made to test this claim in humans in the 1970's but these were usually done shortly at 8-24 hours after injury. We have tried this in animals and found that a myelotomy done during the first 24 hours will allow the spinal cord to swell out of the dura so that we cannot stitch it close. To see the beneficial effects, we must go in at a week or longer, when the spinal cord is not under pressure. When we do a myelotomy at 10 days, the spinal cord does not swell out of the dural opening and the animals show less tissue damage when we look at the spinal cord 6 weeks later.

    I don't know where you got the "understanding" that more than 50% of human spinal cord injuries are much worse than the typical spinal contusions done in the laboratory. In fact, over 64% of spinal cord injuries admitted to hospital in the U.S. are incomplete injuries (ASIA B, C, D). Of those with "complete" spinal cord injuries, almost all involve contusions or crush without penetration of the dura. In ChinaSCINet, I have now seen chronic injured spinal cords in the operating room. You would be astonished by how intact the spinal cord looks. The concept of cutting a chunk of that spinal cord out is, in my opinion, is totally unjustified.

    We are currently testing the hypothesis that umbilical cord blood cells injected into the surrounding cord will migrate into the injury site and produce a bridge of cells. These are of course phase II studies assessing feasibility and safety of the injections. Our studies have shown that the procedure is feasible and safe, that the cells seem to allow bundles of fibers to grow across the injury site and possibly go long distances up and down the spinal cord, and that some of the subjects are recovering locomotor function at 6 or more months after treatment.

    We are not using any biomaterials in our chronic spinal cord injury study. However, there may be an opportunity to use some biomaterials in subacute spinal cord injury. Several groups have approached us with a variety of biomaterials for this purpose. We are still evaluating these materials before we make a decision. As I said, we are planning a phase III trial of the lateral myelotomy treatment of subacute spinal cord injury in ChinaSCINet. If this trial shows that the myelotomy is beneficial, this will open up an opportunity to do a multicenter trial where some type of biomaterial and cells can be placed into the cavity opened up by the myelotomy.

    I do not believe that umbilical cord blood mononuclear cells (UCBMC) will be beneficial for all types of spinal cord injuries. As I have already indicated, this therapy is designed to improve long tract regeneration and may not be effective for some types of spinal cord injuries. For example, UCBMC+lithium, without neuronal replacement therapy, is not likely to help people with lower lumbosacral injuries where substantial gray matter have been damaged. That is why we are now developing a lumbosacral spinal cord injury model and testing neural stem cells in that model with different approaches to attracting axons to grow into the ventral roots.

    On the other hand, I think that the method that we have developed for injecting cells into the spinal cord above and below the injury site will be useful even for severely injured spinal cords, as long as there is no separation of the two ends of the cord. We excluded patients who have long lesion sites where there is a gap of white matter than extends over two segments. This is because we don't want to do a laminectomy that is longer than 2 segments. We have also excluded patients that have T11 and lower injuries or C4 and higher injuries. So, our trial will not shed any light on the efficacy of the therapy for those conditions.

    Wise.
    Last edited by Wise Young; 12-30-2012 at 11:03 PM.

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