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Thread: Dr. Jan-Eric Ahlfors pushes forward with Regeneration Matrix

  1. #251
    Quote Originally Posted by Fly_Pelican_Fly View Post
    Regeneration is a loose term. Highlighting in bold wont give it more meaning. Which spinal tracts are you regenerating? Anything can fall into the term regeneration. What type of axon? What type of neuron? What type of function are you looking for?

    You clearly have your own interpretation of what is means to you but it would be useful for readers to understand so please share in detail. Just citing axons migrating in, through and then out of the injury site and forming functional synapses is not really enough information to describe exactly what you are defining to be regeneration.

    Just out of interest do you consider any of these regenerative?

    http://www.pubfacts.com/detail/23804...nal-cord-injur
    http://www.pubfacts.com/detail/22200...ions-for-regen
    http://www.pubfacts.com/detail/26426...ndroitinase-In
    http://www.pubfacts.com/detail/27019...l-regeneration

    Also, why would you say restoring sensation is impossible? Is the data for the sensation change in the stem cell trial subjects to date a lie? These subjects have been independently assessed before and after intervention from what I understand.
    a) Well to me, to say the spinal cord regenerated means host spinal cord axons, the ones that were damaged upon injury (were "cut" via dieback or knife), have grown in the direction they are supposed to go. Sensory grows toward brain, movement grows down. It doesn't mean they grew back to original targets or even made any functional connections. To say regeneration, that to me would include things like neural stem cells where most of the axon regeneration is from neural stem cells and not host axons. I can't precisely define "substantial regeneration", I guess that's open for personal judgement. I know some treatments are only going to work on certain tracts. But if youre telling me a completely injured rat is walking again, that treatment had better restore tracts responsible for locomotion & sensation, which means long distance regeneration.


    b) I'm not reading all those from Dr. Silver. Dr. Silver's treatment would be considered regeneration if true that host axons are growing through the bridge. I wouldn't use the term "robust" or "substantial" like he does. I'm not convinced that what they saw constitutes return of bladder function. Improved urodynamics does not equate to functional recovery. It might, but I'm not sure.

    See figure 8.H. in "Nerve Regeneration Restores Supraspinal Control of Bladder
    Function after Complete Spinal Cord Injury" by Dr. Silver.

    2 millimeters? How robust. Am I reading this right. An average of 125 fibers made it 1 mm past graft site? 125 fibers? I must be reading this wrong maybe you can clarify that.
    Last edited by Nowhere Man; 05-13-2016 at 06:59 PM.

  2. #252
    c) That study from Mark Tuczynski(sp.) looks like it came out this month. So you can forgive me for not knowing about it. I don't have access to the full paper. Once bitten, twice shy. I remember 4 years go, he came out with a study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445432/ , which reported remarkable axon growth & recovery. "Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery."

    But, when Dr. Oswald Steward’s lab went to replicate it, they couldn’t. Could they get neural stem cells to grow far, yes. But they couldn’t get host spinal cord axons to connect to them. Also, they couldn’t get any functional recovery. “There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocy-tochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.”
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123968/

    So, it will take a lot for me to regain trust in that lab. But it also goes to show that a study is not concrete proof. It needs to be replicated and even then things might not be what they seem.

  3. #253
    Quote Originally Posted by Nowhere Man View Post
    Actually, I am not trying to articulate that. I never said anything about recovery needing to be close to "pre-injury". Regeneration has never been proven to restore ANY function. It has never been proven to restore ANY sensation (probably impossible). It has never been proven to restore any voluntary use of muscle including bladder/bowel. Sure maybe some scientists have CLAIMED to achieve these things, but not in any published & replicated by reputable lab study.

    I'm not a fan, but stem cell Inc. phase 1 trial with safety doses and no rehabilitation component showed and documented sensory improvement after their neural stem cell injection.

  4. #254
    Quote Originally Posted by Mize View Post
    My apologies.

    I know someone in a clinical trial and had been under the impression it was responsible for their recovering hand function. After inquiring i have learned that was not the case. Arm and hand function had returned earlier.
    I know what you're talking about, and it wasn't exactly a clinical trial, just a case study. There were other patients that showed upper body improvements though which is promising. Mind you none of these injuries were very chronic I think the latest was three years

  5. #255
    Quote Originally Posted by Nowhere Man View Post
    c) That study from Mark Tuczynski(sp.) looks like it came out this month. So you can forgive me for not knowing about it. I don't have access to the full paper. Once bitten, twice shy. I remember 4 years go, he came out with a study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445432/ , which reported remarkable axon growth & recovery. "Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery."

    But, when Dr. Oswald Steward’s lab went to replicate it, they couldn’t. Could they get neural stem cells to grow far, yes. But they couldn’t get host spinal cord axons to connect to them. Also, they couldn’t get any functional recovery. “There was extensive outgrowth of GFP labeled axons from the graft, but there was minimal ingrowth of host axons into the graft revealed by tract tracing and immunocy-tochemistry for 5HT. There were no statistically significant differences between transplant and control groups in the degree of locomotor recovery. Our results confirm the previous report that NSC transplants can fill lesion cavities and robustly extend axons, but reveal that most grafts do not create a continuous bridge of neural tissue between rostral and caudal segments.”
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123968/

    So, it will take a lot for me to regain trust in that lab. But it also goes to show that a study is not concrete proof. It needs to be replicated and even then things might not be what they seem.
    This is just my opinion, it's pretty impressive that it "filled" the lesion as for no functional recovery I think that is because proper rehabilitation wasn't given. To cut cost little if any Was probably given. But technically they did replicate the results with substantial axon growth. I want to see high doses of neural stem cells injected at injury site directly, then the patient begins something like the Kumming walking program. Neural stem cells barn none are the superior cells for this issue. Just expensive, potentially dangerous, and difficult to harvest this is why am so interested in this clinical trial if they actually managed to reprogram bone marrow cells to neural. Of course everything is early, as we all know much more funding is needed for all of it

  6. #256
    Quote Originally Posted by JamesMcM View Post
    I'm not a fan, but stem cell Inc. phase 1 trial with safety doses and no rehabilitation component showed and documented sensory improvement after their neural stem cell injection.
    Describe such sensory improvements.

  7. #257
    Quote Originally Posted by JamesMcM View Post
    This is just my opinion, it's pretty impressive that it "filled" the lesion as for no functional recovery I think that is because proper rehabilitation wasn't given. To cut cost little if any Was probably given. But technically they did replicate the results with substantial axon growth. I want to see high doses of neural stem cells injected at injury site directly, then the patient begins something like the Kumming walking program. Neural stem cells barn none are the superior cells for this issue. Just expensive, potentially dangerous, and difficult to harvest this is why am so interested in this clinical trial if they actually managed to reprogram bone marrow cells to neural. Of course everything is early, as we all know much more funding is needed for all of it
    I thought you said animals don't need rehab since their mind is always trying to walk? Pigs did it in Dr. Ahlfors studies..right?

  8. #258
    Quote Originally Posted by Nowhere Man View Post
    a) it is not concrete evidence of regeneration. It can easily be spared intact axons and/or human error. DTI, from what I understand, highlights water movement, its not a picture of the axons. I'm pretty sure other contemporary scientists don't believe it is regeneration either. Isn't chinasci doing another trial right now, to see if untethering & locomoter training alone could be responsible for "walking".? Way too many questions remaining.
    b) return of bladder? Can the patients feel urge of when they have to pee? Not AD, but actual sensation of bladder? Can the patients pee with brain thought alone? Tapping on your bladder is NOT return of bladder function. It's just using spinal cord circuitry. Not the brain. Didn't you say you have been managing your bladder for years by tapping? That's not having bladder function.
    c) Describe the bowel function. What is your concrete evidence of return of bowel? Can the patients feel when they need to go? Can they go on command?
    DTI's were done before, and a few times after the injection. At 6 months, no changes were seen, at 1 year there is clear bundle growth across the injury site and far beyond. 15 of 20 of the subject were able to 'walk' at different levels. 2 of the 5 that didn't walk had to drop out because the pain they felt in their legs turned out to be preexisting fractures. So, walkers could have actually been 17/20. This has never happened in ASIA A subjects before. At the beginning of the trial, two participants were independent for bladder and bowel care but 12 (60 percent) became independent by 41 weeks. Fifty percent were catheter-free at week 41, and 60 percent did not require assistance for bowel management.

    Replication of this trial is necessary, but this absolutely is concrete evidence that it is possible to recover from complete, chronic SCI. This therapy has greatly improved the lives of these people.

    Really, I don't have bladder function?
    Haven't cathed in 19 years, know when I have to go, empty my bladder every time, and haven't had a UTI since my original hospitalization.

  9. #259
    Quote Originally Posted by Jim View Post
    Really, I don't have bladder function?
    Haven't cathed in 19 years, know when I have to go, empty my bladder every time, and haven't had a UTI since my original hospitalization.
    I'm getting more and more excited by what I hear on this.

    Could I ask for a little of the information on how you know when your bladder is full and is it the same for people who recovered bladder function on the trial?

    I get a warm feeling when I need to empty, I suppose this may be mild AD but don't know for sure. When I've had a beer or two I don't notice it though :-(

  10. #260
    Nialle, I know when my bladder begins to get full because I can feel the pressure just like before I was injured.

    I don't know about the trial subjects, that's why we are planning on bringing them back to be examined.

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