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Thread: Stephen Davies Update

  1. #971
    Senior Member Schmeky's Avatar
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    Quote Originally Posted by schmeky
    I want someone to tell me why Davies paper, published April, 2006, entitled, "Astrocytes derived from glial-restricted precursors promote spinal repair", is not in clincal trials?
    Because no one can.

    ________________________________________

    Sprite,

    I am well versed on FDA protocol.

  2. #972
    Thank you FriendlySprite for trying to bring rational, positive thoughts, as well as supporting statements from Davies, to the discussion.

    All I know is there are many talented, hard-working researchers trying to get our butts out of these chairs -- and I'm quite appreciative of their efforts. Personally, I believe Davies is the closest to doing so, but others are making significant progress too.

    From what I've read, I decided last year to stop saying the research efforts should result in legitimate, function-restoring therapies in "five to 10 more years" and now I believe it's realistic to say such therapies should be helping us between 2015 and 2020, which is 4 to 9 years -- and shrinking by the day.

    It helps my peace-of-mind to believe that we are getting closer daily, and to essentially place a limit at 2020 (i.e. 9 more years) tops.

    That said -- what about now? And how do we LIVE from now until such therapies do restore function (and 2020 isn't guaranteed, though I believe it's realistic)?

    My approach has been to get and stay as busy as possible, so that the time will "fly" as quickly as possible. That, and to also enjoy whatever can still be enjoyed, regarding life with an SCI, and though I'm a C1-2 and a vent user, I believe life can still be enjoyed, albeit often from a different perspective than when we were able-bodied.

    Just my two cents.

    Carry on -- and God bless all!

    Bill Miller
    Wheelchair users -- even high-level quads... WANNA BOWL?

    I'm a C1-2 with a legit 255 high bowling game.

  3. #973

    Thumbs up Stephen Davies research has been published!

    From the University of Denver Newsroom

    http://www.ucdenver.edu/about/newsro...rsfocuson.aspx

    Researchers focus on human cells for spinal cord injury repair
    Dervived from stem cells – restore movement in animal models
    3/2/2011
    Stephen Davies

    AURORA, Colo. - For the first time, scientists discovered that a specific type of human cell, generated from stem cells and transplanted into spinal cord injured rats, provides tremendous benefit, not only repairing damage to the nervous system but helping the animals regain locomotor function as well.

    The study, published today in the journal PLoS ONE, focuses on human astrocytes – the major support cells in the central nervous system – and indicates that transplantation of these cells represents a potential new avenue for the treatment of spinal cord injuries and other central nervous system disorders.

    Working together, research teams at the University of Colorado School of Medicine and University of Rochester Medical Center have made a major breakthrough in the use of human astrocytes for repairing injured spinal cords in rats.

    “We’ve shown in previous research that the right types of rat astrocytes are beneficial, but this study brings it up to the human level, which is a huge step,” said Chris Proschel, PhD, lead study author and assistant professor of Genetics at the University of Rochester Medical Center. “What’s really striking is the robustness of the effect. Scientists have claimed repair of spinal cord injuries in rats before, but the benefits have been variable and rarely as strong as what we’ve seen with our transplants.”

    There is one caveat to the finding – not just any old astrocyte will do. Using stem cells known as human fetal glial precursor cells, researchers generated two types of astrocytes by switching on or off different signals in the cells. Once implanted in the animals, they discovered that one type of human astrocyte promoted significant recovery following spinal cord injury, while another did not.

    “Our study is unique in showing that different types of human astrocytes, derived from the exact same population of human precursor cells, have completely different effects when it comes to repairing the injured spinal cord,” noted Stephen Davies, PhD, first author and associate professor in the Department of Neurosurgery at the CU School of Medicine. “Clearly, not all human astrocytes are equal when it comes to promoting repair of the injured central nervous system.”

    The research teams from New York and Colorado also found that transplanting the original stem cells directly into spinal cord injured rats did not aid recovery. Researchers believe this approach – transplanting undifferentiated stem cells into the damaged area and hoping the injury will cause the stem cells to turn into the most useful cell types – is probably not the best strategy for injury repair.

    According to Mark Noble, director of the University of Rochester Stem Cell and Regenerative Medicine Institute, “This study is a critical step toward the development of improved therapies for spinal cord injury, both in providing very effective human astrocytes and in demonstrating that it is essential to first create the most beneficial cell type in tissue culture before transplantation. It is clear that we can not rely on the injured tissue to induce the most useful differentiation of these precursor cells.”

    To create the different types of astrocytes used in the experiment, researchers isolated human glial precursor cells, first identified by Margot Mayer-Proschel, PhD, associate professor of Genetics at the University of Rochester Medical Center, and exposed these precursor cells to two different signaling molecules used to instruct different astrocytic cell fate – BMP (bone morphogenetic protein) or CNTF (ciliary neurotrophic factor) .

    Transplantation of the BMP human astrocytes provided extensive benefit, including up to a 70 percent increase in protection of injured spinal cord neurons, support for nerve fiber growth and recovery of locomotor function, as measured by a rat’s ability to cross a ladder-like track.

    In contrast, transplantation of the CNTF astrocytes, or of the stem cells themselves, failed to provide these benefits. Researchers are investigating why BMP astrocytes performed so much better than CNTF astrocytes, but believe multiple complex cellular mechanisms are probably involved.

    “It is estimated that astrocytes make up the vast majority of all cell types in the human brain and spinal cord, and provide multiple different types of support to neurons and other cells of the central nervous system,” said Jeannette Davies, PhD, assistant professor in the neurosurgery department at the CU medical school and co-lead author of the study. “These multiple functions are likely to all be contributing to the ability of the right human astrocytes to repair the injured spinal cord.”

    With these results, the Proschel and Davies teams are moving forward on the necessary next steps before they can implement the approach in humans, including testing the transplanted human astrocytes in different injury models that resemble severe, complex human spinal cord injuries at early and late stages after injury.

    “Studies like this one bring increasing hope for our patients with spinal cord injuries,” said Jason Huang, MD, associate professor of neurosurgery at the University of Rochester Medical Center and chief of neurosurgery at Highland Hospital. “Treating spinal cord injuries will require a multi-disciplinary approach, but this study is a promising one showing the importance of modifying human astrocytes prior to transplantation and has significant clinical implications.”

    In addition to Proschel and Noble, Davies and Davies, Mayer-Proschel and Chung-Hsuan Shih from the University of Rochester Medical Center contributed to the research. Portions of this research were funded by the New York State Spinal Cord Injury Research Program, the Carlson Stem Cell Fund and private donations by the international spinal cord injury community.

    # # #

    Contact: Dan Meyers, 303-724-5377, dan.meyers@ucdenver.edu
    "Our lives begin to end the day
    we become silent about things that matter."
    - Martin Luther King Jr

  4. #974
    Thanks Donna! Way to keep watch for us!

    http://www.cufund.org/giving-opportu...ption/?id=3485 to contribute to Dr. Stephen Davies research lab.


    Home page:

    http://www.cuneurosurgery.com/research-davies.htm
    Last edited by GRAMMY; 03-02-2011 at 11:07 PM.

  5. #975
    Thanks Chris! I'm just trying to keep up with you. : )

    For those of you who would like to see his video from W2W, here is the link.
    "Our lives begin to end the day
    we become silent about things that matter."
    - Martin Luther King Jr

  6. #976
    Senior Member mikek's Avatar
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    Impressive news !!! I wonder how long the next step will take before human trials ??

  7. #977

    Here is the abstract

    http://www.plosone.org/article/info%...l.pone.0017328

    Stephen J. A. Davies1, Chung-Hsuan Shih2, Mark Noble2, Margot Mayer-Proschel2, Jeannette E. Davies1#*, Christoph Proschel2#
    1 Department of Neurosurgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, United States of America, 2 Department of Biomedical Genetics, Institute for Stem Cell and Regenerative Medicine, University of Rochester Medical Center, Rochester, New York, United States of America
    Abstract Top

    Repairing trauma to the central nervous system by replacement of glial support cells is an increasingly attractive therapeutic strategy. We have focused on the less-studied replacement of astrocytes, the major support cell in the central nervous system, by generating astrocytes from embryonic human glial precursor cells using two different astrocyte differentiation inducing factors. The resulting astrocytes differed in expression of multiple proteins thought to either promote or inhibit central nervous system homeostasis and regeneration. When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. In marked contrast, human glial precursor cells and astrocytes generated from these cells by exposure to ciliary neurotrophic factor both failed to promote significant behavioral recovery or similarly robust neuronal survival and support of axon growth at sites of injury. Our studies thus demonstrate functional differences between human astrocyte populations and suggest that pre-differentiation of precursor cells into a specific astrocyte subtype is required to optimize astrocyte replacement therapies. To our knowledge, this study is the first to show functional differences in ability to promote repair of the injured adult central nervous system between two distinct subtypes of human astrocytes derived from a common fetal glial precursor population. These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes. In addition, our studies provide a specific population of human astrocytes that appears to be particularly suitable for further development towards clinical application in treating the traumatically injured or diseased human central nervous system.


    More here.....
    "Our lives begin to end the day
    we become silent about things that matter."
    - Martin Luther King Jr

  8. #978
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    Quote Originally Posted by IMHopeful View Post
    http://www.plosone.org/article/info%...l.pone.0017328

    Stephen J. A. Davies1, Chung-Hsuan Shih2, Mark Noble2, Margot Mayer-Proschel2, Jeannette E. Davies1#*, Christoph Proschel2#
    1 Department of Neurosurgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, United States of America, 2 Department of Biomedical Genetics, Institute for Stem Cell and Regenerative Medicine, University of Rochester Medical Center, Rochester, New York, United States of America
    Abstract Top

    ...... When transplanted into acute transection injuries of the adult rat spinal cord, astrocytes generated by exposing human glial precursor cells to bone morphogenetic protein promoted significant recovery of volitional foot placement, axonal growth and notably robust increases in neuronal survival in multiple spinal cord laminae. .....


    More here.....
    More power to Dr. Davies and other authors. However, it is still a paper about acute transection injury of the adult rat. The injury model is neither chronic nor a contusion. He has published a similar paper years ago using rat/mouse astrocytes. I don't know how far he is from chronic studies with Decorin and/or human astrocytes. Probably the proverbial five years.

  9. #979
    I hope this isnt the big news we been waiting on.

  10. #980
    Senior Member kate's Avatar
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    Quote Originally Posted by Quad62 View Post
    More power to Dr. Davies and other authors. However, it is still a paper about acute transection injury of the adult rat. The injury model is neither chronic nor a contusion. He has published a similar paper years ago using rat/mouse astrocytes. I don't know how far he is from chronic studies with Decorin and/or human astrocytes. Probably the proverbial five years.
    The breaking news is that he was able to do with human cells what he had done in 2006 with rat cells:

    These findings are consistent with our previous studies of transplanting specific subtypes of rodent glial precursor derived astrocytes into sites of spinal cord injury, and indicate a remarkable conservation from rat to human of functional differences between astrocyte subtypes.
    They obviously couldn't go to human clinical trials with rat-derived astrocytes; there had to be studies done to show that human-derived astrocytes worked just like the rat-derived ones did, in rats, before any trials could be designed to put the human-derived ones into humans.

    The words "remarkable conservation from rat to human" are very good news in the sense that this therapy has passed a test in working across species.

    As far as the restriction in this paper to acute transections . . . I think it was a good choice. Acute, because keeping transected rats alive for many months doesn't make sense unless you already know it works on new injuries. Transections, because functional recovery from a transected cord is damn hard to argue with.

    In addition, our studies provide a specific population of human astrocytes that appears to be particularly suitable for further development towards clinical application
    The lab work that went into this paper was probably finished as long as two years ago . . . the peer review process is molasses in January, to quote my Irish mom. I am 100% sure that the "further development towards clinical application" -- which will be targeted at chronic contusion injuries -- has been underway all along.

    No one who has met Steven Davies doubts his enthusiasm for getting to the finish line . . . and I say that as someone who is about to mark the 10th anniversary of the day sci blew up my family's life. It can't come fast enough.

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