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Thread: Stem cell therapy for spinal injury

  1. #1

    Stem cell therapy for spinal injury

    http://www.scienceblog.com/cms/node/6979

    Researchers at Karolinska Institutet have shown how the transplantation of stem cells improves recovery from spinal injury. However, a painful condition can also develop, which can be prevented if the stem cells are supplemented with a certain gene that controls their maturing process. The results are important for planning of stem cell therapy trials on patients with spinal injury.

    Spinal injury confines some 150 Swedes a year to wheelchairs. The damage cause the loss of movement and sensation below the level of injury. A research team at Karolinska Institutet has now shown using rat models that the introduction of stem cells following such injury is effective, although a double-edged sword: while on the one hand the injection of stem cells into the damaged area of the spine improves motor function (movement) inferior to the injury level, scientists found that the rats developed greater pain sensitivity just superior of it.

    In a follow-up study, a special gene, neurogenin-2, was added to the stem cells while they were developing in culture. When stem cells containing this gene were transplanted into the damaged spinal cord, the adverse pain effects failed to appear while the enhancement of motor function improved. Sensory function (feeling) below the injury also clearly improved.

    The aggravated sensitivity to pain was thought to be the result of the fact that many stem cells developed into astrocytes, a kind of glial cell that encourages the growth of pain axons in the spinal cord by secreting substances that stimulate neuronal development.

    The researchers found that the presence of neurogenin-2, a "transcription factor" that regulates the activity of other genes during the stem cell maturing process, inhibited the development of astrocytes and encouraged the formation of oligodendrocytes, another type of glial cell that forms the fatty myelin sheaths around the axons. The small number of astrocytes that developed from the neurogenin-2-bearing stem cells corresponded to the lack of growth of pain axons. The greater number of oligodendrocytes that were produced by the neurogenin-2-bearing stem cells also corresponded to a greater volume of white substance, i.e. myelin coated nerve fibres, in the damaged area.

    With the help of functional Magnetic Resonance Imaging (fMRI), the team, working from KI's experimental MRI centre, has managed for the first time to demonstrate the return of sensory function following spinal injury. An advantage of the fMRI technique is that it can be used to compare results from animal and human studies if and when new therapies for the treatment of spinal injury can be tested on patients.

    Publication:
    Allodynia limits the usefulness of intraspinal neural stem cell grafts and directed differentiation improves outcome
    Christoph Hofstetter, Niklas Holmström, Johan Lilja, Petra Schweinhardt, Jinxia Hao, Christian Spenger, Zsuzsanna Wiesenfeld-Hallin, Shekar Kurpad, Jonas Frisén, Lars Olson
    Nature Neuroscience Online February 13, 2005
    In print: Nature Neuroscience March 2005

    For more information, please contact:
    Professor Lars Olson, Department of Neuroscience, Karolinska Institutet,
    phone +46 8 524 870 50, +46 70 670 3388 or mail lars.olson@neuro.ki.se

    From Karolinska Institutet

  2. #2
    Here is the abstract to the study:

    Hofstetter CP, Holmstrom NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, Wiesenfeld-Hallin Z, Kurpad SN, Frisen J and Olson L (2005). Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci Several studies have reported functional improvement after transplantation of neural stem cells into injured spinal cord. We now provide evidence that grafting of adult neural stem cells into a rat thoracic spinal cord weight-drop injury improves motor recovery but also causes aberrant axonal sprouting associated with allodynia-like hypersensitivity of forepaws. Transduction of neural stem cells with neurogenin-2 before transplantation suppressed astrocytic differentiation of engrafted cells and prevented graft-induced sprouting and allodynia. Transduction with neurogenin-2 also improved the positive effects of engrafted stem cells, including increased amounts of myelin in the injured area, recovery of hindlimb locomotor function and hindlimb sensory responses, as determined by functional magnetic resonance imaging. These findings show that stem cell transplantation into injured spinal cord can cause severe side effects and call for caution in the consideration of clinical trials. Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.

  3. #3
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    Stem Cell Therapy For Spinal Injury

    Stem Cell Therapy For Spinal Injury
    Researchers at Karolinska Institutet have shown how the transplantation of stem cells improves recovery from spinal injury. However, a painful condition can also develop, which can be prevented if the stem cells are supplemented with a certain gene that controls their maturing process. The results are important for planning of stem cell therapy trials on patients with spinal injury. Spinal injury confines some 150 Swedes a year to wheelchairs. The damage cause the loss of movement and sensation below the level of injury. A research team at Karolinska Institutet has now shown using rat models that the introduction of stem cells following such injury is effective, although a double-edged sword: while on the one hand the injection of stem cells into the damaged area of the spine improves motor function (movement) inferior to the injury level, scientists found that the rats developed greater pain sensitivity just superior of it.
    http://www.sciencedaily.com/releases...0218130441.htm



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