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Thread: Stretching?

  1. #1

    Stretching?

    Any opinion ??
    Tissue Engineering Journal Reports Success in Stretching Nerve Axons to Bridge Nerve Damage, Spinal Injuries

    By datamaster, linked from Yahoo Biotech

    A new method of stretching nerve tissue that has the potential for repairing spinal cord and other central nervous system injuries has been devised by a team of scientists from the University of Pennsylvania in Philadelphia. Their work is reported in the April (Volume 7, Number 2) issue of Tissue Engineering, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com). The paper is available free online at www.liebertpub.com/ten.
    ``A New Strategy to Produce Sustained Growth of Central Nervous System Axons: Continuous Mechanical Tension,'' by Douglas H. Smith, M.D., and John A. Wolf, B.S., of the university's Department of Neurosurgery and David F. Meaney, Ph.D., of the Department of Bioengineering, describes the authors' success in coaxing central nervous system (CNS) nerve cell connections, or axons, to grow and stretch in response to continuous mechanical tension. Such elongated axons could be implanted into damaged or severed spinal cords to bridge gaps caused by injuries, restoring communication up and down the spine.


    This strategy has long been used in humans, but producing axons of sufficient length and number has posed a significant challenge until now. Smith, Wolf, and Meaney grew human nerve cells on two plastic slabs sandwiched together; gradually pulling the slabs apart using a microstepper motor system to separate the membranes. This axon stretching method produced half-inch-thick bundles of thousands of axons that grew a remarkable one centimeter in length after ten days of stretching.


    ``This is the first evidence that the center portion of synapsed CNS axons can exhibit sustained stretch-induced growth,'' say the authors, who propose that this newfound growth ability of integrated CNS axons may be exploited to produce transplant materials to bridge extensive nerve damage.


    ``We're making jumper cables,'' said Dr. Smith, a neurosurgeon who is an expert on traumatic brain injury, in a story by Sandra Blakeslee in The New York Times on April 17. Dr. Smith and his colleagues are now implanting the axons into animals with severed spinal cords with promising results, but the use of this methodology in humans has yet to be tested. ``People are a lot more complicated,'' said Dr. Smith.


    ``This research supports one of the key repeating themes of Tissue Engineering: that to be successful, you should mimic mother nature,'' commented journal Co-Editor Charles A. Vacanti, M.D., of the University of Massachusetts Medical Center. ``Mechanical tension appears to be a significant factor in determining the elongation of axons in human growth and development.''


    Tissue Engineering is the authoritative peer-reviewed journal, published in print and online, that focuses on the engineering of new biologic tissues, covering the fields of biomedical engineering, materials science, molecular and cellular biology, and reconstructive surgery. It is the official journal of the Tissue Engineering Society and the British, European, and Asian Tissue Engineering Societies and is indexed in Index Medicus/MEDLINE. The bimonthly journal is co-edited by Dr. Vacanti and Antonios G. Mikos, Ph.D. For a complete table of contents, a free sample issue, or to subscribe, visit www.liebertpub.com/ten.
    Mary Ann Liebert, Inc., is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Human Gene Therapy and e-biomed: The Journal of Regenerative Medicine. Its biotechnology trade magazine, Genetic Engineering News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 60 publications is available at www.liebertpub.com.
    --------------------------------------------------------------------------------

  2. #2
    On the surface, this finding may not seem to be all that relevant to spinal cord injury but Doug Smith has a really nice idea that I like a lot. Basically, he is thinking of taking a bunch of neurons in culture, getting them to grow axons in one direction, and then stretching those axons to grow long distances. These could then form an entire motor unit that they can then transplant into the spinal cord and insert the axons into a muscle. They haven't really gotten that to a point of practical application yet but I think that it is one of the best options that I have heard to date, for replacing motoneurons and getting them to innervate muscles.

  3. #3

    stretching axons

    I think this research will be very valuable and I hope this group has plenty of funds to continue work and collaborate findings and form practical applications for the use of functional recovery for the spinal cord injured. I have been trying to keep up with new discoveries for 29 years and I hope this will lead to something that can be applied within the next 2 years. There has to be a better way to get things done. If the axon stretching research is promising, please let us make sure it it is supported.

  4. #4

    Agreed

    This sounds very promising. My guess is that, when applied to humans, this would involve some pretty invasive surgical procedure?

    Wise, if proven successful this may eliminate the need for axon directional guidance mechanisms (a big challenge you've previously discussed) such as the collagen tubes, scaffolding being developed by I believe the Miami project?

    My understanding is that axonal growth is being achieved by you and your colleagues but getting them to grow to their intended target has proven difficult? This theory, discussed above, sounds more like once the axon is stretched then it could be surgically applied / implanted and becomes an axonal / nerve "splice"? Given successful implantation the next logical step would be remyelination, then reinervation etc.?

    Am I way off base here?

    Thanks

  5. #5

    I'll believe it when I see it!

    Dr. Young,

    I believe I have become a pessimist. I keep reading all of these research articles that come very close to saying they have a cure for CNS disorders. However, ineffiably they end the article with, "however we haven't tried it on humans," or "human studies are years away," etc. I wonder if part of the problem is that once they actually find the answer they realize that their funding will stop and they will be out of jobs so they draw out the research. I know that due to the struggle of being a quad that I may have become jaded but it seems to be the case in just about every promising cure.

    Realistically as a scientist and Doctor how long do you think it will be till we can burn our wheel chairs? No sugar coating please.

    Thanks,

    Debbie

  6. #6
    Super Moderator Sue Pendleton's Avatar
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    So this stretching is more to repair lower motor neurons than upper motor neurons, Wise?

  7. #7
    Debbie7, There is something at the banquet table for everybody. Here goes another list...

    In the coming 1-3 years, I am hoping that
    • 4-aminopyridine is approved,
    • AIT-082 will show good results
    • porcine stem cells show good results
    • copaxone will get into clinical trial soon
    • rolipram will get into clinical trial soon
    • IN-1 will get into clinical trial soon
    • OEG transplants start in U.S.
    • Human adult stem cells start in the US
    • chondroitinase ABC infusion starts trial
    • supported ambulation training is proven to restore locomotor function
    • central pattern generator stimulator is used.
    I believe that these treatments will produce some recovery in some people. These are first generation therapies.

    In the mid-term, 3-6 years, I am anticipating that the second generation therapies will come out, i.e.
    • Nogo receptor blockers goes to trial
    • C3 or other rho blockers go into clinical trial
    • a second generation therapeutic vaccine
    • human embryonic stem cells
    • and various combination of the best of the first generation therapies

    We might get real unlucky and none of the treatments work but I don't believe in bad luck if we do our job right, in the same way I don't believe in good luck.

    L. J. Webber and Chris, the axon stretching is not necessary for regeneration of the spinal cord. In my opinion, it is a very interesting approach to replacing motoneurons. As you know, many people who have L1-L2 injury have damaged their motoneurons and I have been worried about how these neurons can be replaced. Note that the treatment not only has to replace the neuron but get it to grow out the peripheral nerve to the muscle. The muscle will be atrophic, etc. Therefore, it seemed like a lot of hurdles and I was not particularly sanguine about the possibility that motoneuron replacement will be possible any time soon.

    In my opinion, the stretching idea is not as important as the idea of creating a whole motor unit with peripheral nerve outside the body and then transplanting the unit into the cord and connecting it to muscle. The stretching is just a way of getting the unit to grow faster. By the way, we still have not solved the problem of the atrophic muscle. However, we take one step at a time.

    Wise.

  8. #8
    Senior Member X-racer...'s Avatar
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    DR. Y i noticed you didn't mention M1, or L1 in your 1-3yr and 3-6yr comments. any comment????


    LIVE IT UP AND LIVE IT LARGE!!!!

  9. #9
    X-racer,

    I should put a list all the therapies on my clipboard so that I don't have to pull it out of my head every time... There are so many therapies that I can no longer rattle them off. M1 is going into clinical trial for MS. We still have to find a form of soluble L1 that consistently works. However, please note that OEG cells are a form of super L1 therapy. In addition to secreting a bunch of neurotrophins (NGF, BDNF, neuroregulin), it also expresses L1 on its surface, exactly what you would like the L1 to be on... a migrating cell that races alongside the growth cones, squirting neurotrophins at them.

    Wise.

    1. Boruch AV, Conners JJ, Pipitone M, Deadwyler G, Storer PD, Devries GH and Jones KJ (2001). Neurotrophic and migratory properties of an olfactory ensheathing cell line. Glia. 33 (3): 225-9. Summary: Olfactory ensheathing cells (OECs) are a unique type of macroglia required for normal olfactory axonal regeneration throughout the lifetime of an individual. Recent evidence in the literature suggests that OECs transplanted into injured spinal cords may facilitate axonal regeneration. In this study, we evaluated the neurotrophic properties of OECs using a homogeneous clonal cell line (nOEC), which does not contain contaminating cell types found in all primary OEC cultures. The results indicate that nOECs express mRNA for NGF, BDNF, NT-4/5, and neuregulins, but not for NT-3 or CNTF. In addition, nOECs secrete NGF, BDNF, and neuregulin, but retain NT-4/5 intracellularly. Finally, prelabeled nOECs derived from rat survived transplantation into a dorsal hemisected region of the hamster spinal cord and migrated only in the injured, dorsal portion of the spinal cord. This migratory pattern suggests that the nOECs are viable in vivo and respond to signals originating from the injured neuronal cells and their processes. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&li st_uids=11241740> Department of Cell Biology, Neurobiology, and Anatomy, Stritch School of Medicine, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.


    Wise.

  10. #10
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    Another way to look at it

    Debbie 7, I've also become cautious about optimistic-sounding reports that cures are on the way. I'm 50 and have hepatitis C. I'm starting to despair over possible cures for me.

    You're right, too many of these ideas are in the animal stages of experimentation where they can stay forever. That's why SPIs are susceptible to any possibility of a cure. Notice the intense interest in Dr. Kao's procedures, which may be years from occuring in the United States. We're vulnerable, like terminal cancer patients who go to Mexico and other places for cures that are not to be.

    Two luminous problems are objectivity and funding. Some companies report progress toward an SPI cure because it's to their financial advantage.

    What we need is more federal funding for medical research. But the Bush administration prefers massive increases in military spending to substantial increases in medical funding. We have to elect politicians that support these increases.

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