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Thread: Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells

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    Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells

    Proc Natl Acad Sci U S A 2002 Feb 26; [epub ahead of print]


    Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells.

    Teng YD, Lavik EB, Qu X, Park KI, Ourednik J, Zurakowski D, Langer R, Snyder EY.

    Departments of Neurology, Pediatrics, and Neurosurgery, Harvard Medical School, Boston, MA 02115; Harvard--MIT Division of Health Sciences and Technology, and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; and Departments of Orthopaedic Surgery and Biostatistics, Children's Hospital, Boston, MA 02115.

    To better direct repair following spinal cord injury (SCI), we designed an implant modeled after the intact spinal cord consisting of a multicomponent polymer scaffold seeded with neural stem cells. Implantation of the scaffold--neural stem cells unit into an adult rat hemisection model of SCI promoted long-term improvement in function (persistent for 1 year in some animals) relative to a lesion-control group. At 70 days postinjury, animals implanted with scaffold-plus-cells exhibited coordinated, weight-bearing hindlimb stepping. Histology and immunocytochemical analysis suggested that this recovery might be attributable partly to a reduction in tissue loss from secondary injury processes as well as in diminished glial scarring. Tract tracing demonstrated corticospinal tract fibers passing through the injury epicenter to the caudal cord, a phenomenon not present in untreated groups. Together with evidence of enhanced local GAP-43 expression not seen in controls, these findings suggest a possible regeneration component. These results may suggest a new approach to SCI and, more broadly, may serve as a prototype for multidisciplinary strategies against complex neurological problems.

  2. #2
    Senior Member kate's Avatar
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    excellent news

    Wow. Did I just really read that? 1 year post injury, those little rats were really marching around? Let's get those clinical trials going!

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    That's an AWESOME post Seneca...where can we get a copy of the whole Journal article? The thing is, I wonder what the success rate is. My bet is that a therapy like this is unidirectional. A person can only have so many polymer scaffolds injected.

    Eric Texley

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    Greetings

    Once again, another report which does not disclose acute or chronic time frames.
    "70 days post injury" does not say if the polymer bridge was implanted 1 day or 1 month after injury.
    Unfortunately, I suspect 1 day over the latter.

    Paul

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    At first glance this paper is very exciting. But you'll notice the authors don't mention how soon after injury they implanted their matrix. However, by telling us they attribute the functional improvements exhibited by the treated group to reduced secondary injury and less glial scarring, they're letting us know the animals were treated at a very acute stage...definitely not chonics! This statement also tells us that they do NOT attribute the functional improvement to massive regeneration of new axons through their matrix...they merely say that "some" axons were observed passing through areas in the treated animals that were absent in the controls. In other words, at this point this procedure is more neuroprotective than regenerative, which would only apply to new injuries prior to secondary injury...at a very early traumatic stage.

    These results are inferior to Neurogel's, which allowed acutely injured cats to completely regain the ability to walk after a section of their spinal cord was removed and immediately replaced by Neurogel. However, in chronic models Neurogel implantation only resulted in a 5% bbb functional improvement. (Neurogel had both growth factors and stems cells imbedded in its matrix). These scaffoldings (Neurogel and the one presented below) both seem to provide a degree of bridging across the lesion, but they do not cause a massive axonal regenerative response to cross it!

    What must now be done is to combine this matrix with something that will initiate robust new growth, such as inosine, AIT-082, or certain growth factors, then prove its usefullness in chronic contusion injuries (not acute hemisections) before it will do any of us any good.

    James Kelly

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    Member Al Bundy's Avatar
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    Harvard and the Children's Hospital

    If you look around the CRISP database at the NIH and the U.S. Patent Office, you will see that Harvard and the Children's Hospital are experimenting aggressively with growth factors, stem cells, and polymers. Coming from Harvard, it may be the latest thing or just the flavor of the month. I imagine they are developing something for every indication you can think of.

    Allen
    baudi73@yahoo.com

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    Eric, I don't have access to the full text. Maybe Dr. Young could post it once it's published. I think the abstracts are released before the actual articles are.

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    Senior Member Jeff's Avatar
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    Another problem with this study is their injury model

    A hemi-section is not completely relevant. Most of us have contusion injuries which are a different animal, so to speak.

    ~See you at the SCIWire-used-to-be-paralyzed Reunion ~

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    Member Al Bundy's Avatar
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    Everything I Know About Harvard, Evan Snyder, And the Children's Hospital

    First, Larry Benowitz at Harvard is the lead researcher on Inosine and AF-1. We all know that. If you go to the CRISP Database at the NIH you will see that Dr. Benowitz is currently working on a combinational therapy of stem cells and growth factors. Speaking of stem cells, Dr. Evan Snyder, I think, discovered and patented the first line of neural stem cells which is now owned by Layton BioSciences. This study in the Proceedings of the National Academy Of Sciences interests me. I would like to know where Layton is in their neural stem cell research. I wonder whose stem cells were used in this study. I'm sure I will end up contacting them myself. Unless there are any other volunteers. Finally, with regard to the Children's Hospital, I remember reading through some patents and I saw that the Children's Hospital has a patent on its own PEG technology. I imagine all of the technologies used in this study are associated with these groups.

    Allen
    baudi73@yahoo.com

  10. #10
    The Proceedings of the National Academy of Science is available to people who have subscriptions. They have an early eprint edition but one unfortunately needs to pay
    http://www.pnas.org/papbyrecent.shtml

    I will go through the paper and try to answer all the questions in detail tomorrow.

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