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Thread: ASAS Following Recoarctation of Aorta

  1. #11
    Super Moderator Sue Pendleton's Avatar
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    Quote Originally Posted by mark75
    I would just like an outside opinion regarding Dr. Huang's work from someone who is familiar with it. I don't think that I am eligible for any of the other programs that use autologous OEG's. At present, Dr. Huang is the only one who has accepted me as a candidate. You thoughts would be very much appreciated.

    Mark
    I'm curious if Mark were to go to China and have this procedure would Dr Huang be amenable to his asking for anti-rejection drugs as a trial of 1 based on what results have shown to date, Wise? I realize that those drugs are both expensive and have their own serious side effects especially if needed long term.

    Mark, is there a specific reason you think you would not be a candidate for a trial, if one were currently available, using your own OE cells? Obviously a coarction is different from many of the atraumatic injuries but not when you look at the end result of return of sensation/propriosensation and light touch/vibration but no or little movement. Just want to get another's view on this. Thanks.
    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.

  2. #12
    Sue,
    I don't see any reason why I wouldn't be a candidate in a procedure using my own cells, but so far I haven't been able to find anyone else doing this procedure on atraumatic injuries. I always come up disqualified due to the type of injury I have, my age, time since the injury, etc. And I understand that many of the these trials are aimed at studying the effects of this procedure on specific situations. Therefore, at this point in time, it seems that Dr. Huang's procedure is the only one that would accept me as a patient, and as Dr. Young has already pointed out, there is the risk of immunological rejection since the cells are not coming from me. I think the CoA is irrelevent in my case, because my ASAS is a secondary problem to the CoA, albeit it was certainly the cause of the paralysis. I have tried to find other studies of patients who have had paralysis following this surgery and study their long-term results. In seven years of looking I have come up short; perhaps I am just not looking in the right places, but I can't seem to find anything.

    One question regarding your post, Sue: Is there a reason based on Dr. Huang's results that I should request immuno-suppressant medication following this procedure? The reason I ask is that I have been under the impression that so far, no one has had an issue with tissue rejection. Am I right or wrong about this?

  3. #13
    Super Moderator Sue Pendleton's Avatar
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    Quote Originally Posted by mark75
    Sue,
    One question regarding your post, Sue: Is there a reason based on Dr. Huang's results that I should request immuno-suppressant medication following this procedure? The reason I ask is that I have been under the impression that so far, no one has had an issue with tissue rejection. Am I right or wrong about this?
    In Wise's post under number 6 below (posts are numbered on the right upper corner of each) he mentions that immune rejection may be a concern when the cells are not matched even if fetal in nature.
    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.

  4. #14
    Sue,
    I understand that immunological rejection is possible, but I am wondering if it has ever happened in Dr. Huang's procedure. My understanding is that he has performed this procedure on 600+ individuals; not sure how many of them are American. And Dr. Huang posits that fetal cells are not rejected; therefore, I wonder 1.) Has it ever happened with any of his procedures? and 2.) If not, how many individuals must have the procedure with no immunological rejection before this is considered to be true. To my knowledge, no one has experience any tissue rejection from this procedure, unless there are figures I am unaware of. I would feel more comfortable without the immunosuppressants knowing that no one else has ever experienced tissue rejection. By the way, my understanding is that in China, the cost of the immunosuppressants are higher than the cost of the surgery. Thoughts??

  5. #15
    Quote Originally Posted by mark75
    Sue,
    I understand that immunological rejection is possible, but I am wondering if it has ever happened in Dr. Huang's procedure. My understanding is that he has performed this procedure on 600+ individuals; not sure how many of them are American. And Dr. Huang posits that fetal cells are not rejected; therefore, I wonder 1.) Has it ever happened with any of his procedures? and 2.) If not, how many individuals must have the procedure with no immunological rejection before this is considered to be true. To my knowledge, no one has experience any tissue rejection from this procedure, unless there are figures I am unaware of. I would feel more comfortable without the immunosuppressants knowing that no one else has ever experienced tissue rejection. By the way, my understanding is that in China, the cost of the immunosuppressants are higher than the cost of the surgery. Thoughts??
    Mark, it is often hard to tell when cells have been rejected from the central nervous system. In fact, there are some scientists who believe that the rejection itself, with its accompanying inflammation, may stimulate neurotrophin expression in the spinal cord and thereby stimulate more axonal growth. Note that if the olfactory ensheathing glia are acting as a "bridge" for axonal growth, elimination of that bridge after the axons have grown across may not (should not) be associated with loss of function. So, one cannot use functional decline as a means of detecting immune rejection of the cells. Finally, there is a possibility that immune suppression may suppress axonal growth or, alternatively, it may promote axonal growth because cyclosporin has been reported to do that in animals. So, it is very hard to tell. Unfortunately, there have been no autopsies of any human that has received olfactory ensheathing glia.

    Even if there had been autopsies, it may be difficult to tell what has regenerated versus what was already there before the surgery. Olfactory ensheathing glia don't have unique markers so that they can be easily distinguished from native cells. For example, while animal olfactory ensheating glia do express P75 (a receptor for NGF) and GFAP (a glial marker), and this combination is often regarded as a definitive marker for OEG cells since no other cells in the central nervous system should express both of these markers, recent studies (not yet published from my laboratory) suggests that human OEG cells do not express GFAP. Schwann cells express P75 but not GFAP, do invade into injured spinal cords from spinal roots, and may be mistakened for OEG cells. Finally, we have shown that when rat OEG cells myelinate axons, they lose their P75. So, neither the P75 or GFAP markers are reliable markers of OEG. So, even if there is an autopsy, it may be difficult to tell whether the cells have survived in the spinal cord and therefore provide rigorous test of the hypothesis that fetal OEG cells are not rejected from the spinal cord.

    One possible approach that is now being worked on is to mark the cells before transplantation. Several studies have shown that it is possible to put paramagnetic beads into transplanted cells and these beads can be tracked by MRI scans. However, when the cells die, the beads will still be there in the spinal cord and therefore this may be misleading. There is work on making biodegradable paramagnetic beads but I don't know how far that has gone. Another possibility is to insert a gene so that the transplanted cells makes a specific marker, including paramagnetic proteins. This is something that is obviously crucial to the transplantation field. If we are able to determine the survival and migration of transplanted cells, this would be a great boon to interpreting the results of cell transplants.

    I know that Dr. Huang has been trying very hard to do HLA-matching of fetuses so that he can at least try to transplant cells into patients that have partial HLA-matches, in order to reduce the probability of immune rejection. However, it is very difficult to do matching with so few cells. The aborted fetuses become available a few at a time and he doesn't have many to choose from. While he does have many patients to choose from, the cost of doing HLA matching in all his patients is prohibitive. Finding immune-compatible OEG cells for transplantation is a difficult task. I am not sure that it can be done in this way.

    We have been considering this problem in the ChinaSCINet. My preliminary conclusion is that we should not be doing OEG transplants in the clinical trials of ChinaSCINet next year for three reasons:
    1. There are limits to the number of fetuses that can be obtained in any given time period and I am not sure that we will be able to get enough for the clinical trial.
    2. Quality control of the cells would be very difficult to attain. We would have to set up a facility that conforms to good manufacturing practice (GMP) standards to provide the cells to all the centers.
    3. Immune-matching of random fetal tissues to patients will not be possible. We must be able to ensure immune-compatibility of the transplanted cells.

    For that reason, we are currently considering either bone marrow or umbilical cord blood stem cells. The animal data behind either of these being beneficial in spinal cord injury is not as strong as for OEG cells. On the other hand, I am also thinking that it is important to test umbilical cord blood or bone marrow stem cells because there are so many places around the world doing either of these transplants and claiming that they are effective. So, this will be a subject of considerable discussion and interest at the upcoming International Spinal Cord Injury Treatment and Trials (http://ISCITT.org) symposium in Hong Kong. I am hoping that the combined expertise and wisdom of the people at the meeting will help us reach a consensus concerning the best therapy to test in the upcoming trials.

    Wise.

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