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Implanting olfactory ensheathing glial cells into the spinal cords of paralyzed adult rats recently has been shown to promote neuronal cell repair and restore function. After transplantation, the rats were able to walk, even climb over complex terrain, and respond to touch and proprioception (stimuli originating in muscles and tendons) in their hind-limbs. These results are the most dramatic functional and histological repair yet achieved after complete spinal cord transection in adult mammals, and they open new avenues in the search for treatment of spinal cord injuries in other mammals, including humans.
The leader of the group of scientists who achieved this, Dr. Almudena Ramon-Cueto, Institute of Biomedicine, Spanish Council for Scientific Research in Valencia, is one of a panel of experts speaking in New Orleans April 22 at an Experimental Biology 2002 American Association of Anatomists symposium on Olfactory Ensheathing Cells: Therapeutic Potential in Spinal Cord Injury. Chaired by Dr. Kathryn J. Jones, Loyola University in Chicago, the panel discusses the location and structure olfactory ensheathing cells, how they work, and why the best hope for restoring function in human spinal cord injury patients might well lie in their own noses.
Dr. Ramon-Cueto presents the data from her adult rat study and discusses the advantages of using olfactory ensheathing glia to treat spinal cord injuries in mammals. An important one, she says, is that these cells can be obtained from adult donors, offering the possibility of auto-transplantation. If this technique had a future application in humans, the patient could be his or her own donor. Using the patient’s own plentiful supply of these olfactory ensheathing cells would resolve problems with tissue availability as well as the need for immune system suppression to avoid rejection of foreign tissue. The cells also hold great promise in overriding the usual hostility of the brain and spinal cord of adult mammals to axon regeneration, which has always been a big problem for the design of therapeutic approaches to treating spinal cords. Dr. Ronald Doucette, University of Saskatchewan, explains this promise.
In animals, including humans, the nerve small cells in the nasal passages that detect odors in the air we breathe (i.e. the olfactory neurons) die and are replaced at regular intervals. The nerve fibers of these newly-formed neurons grow within the olfactory nerve and eventually connect with the olfactory bulb (i.e. the part of the brain concerned with smell). The success with which this reconnection happens is why we do not normally detect any loss of smell even though the neuronal recycling is an ongoing event in each and every one of us. How these nerve fibers accomplish this task in adult mammals is not known for sure, especially given the relatively inhospitable environment for nerve growth in other parts of the brain and spinal cord. Dr. Doucette describes how olfactory ensheathing cells are believed to play a significant role in providing a friendly environment through which the olfactory nerve fibers can grow to make connections with the olfactory bulb. These glial cells ensheathe or envelope the nerve fibers of the unmylineated olfactory nerves along the entire extent of the nerve from the origin of the nerve in the nose to their termination in the olfactory bulb. He next talks about the role these cells play in the unusual plasticity observed in this area of the brain of adult mammals, that is, how they are believed to facilitate the growth of olfactory nerve fibers into the brain.
When he next describes the migratory ability of olfactory ensheathing cells to move toward demyelinated areas of the spinal cord, he will explain why he believes these cells are a clinically relevant alternative to Schwann cells for the repair of the injured spinal cord and the treatment of demyelinating diseases like multiple sclerosis. He also discusses some of the obstacles yet to be overcome before olfactory ensheathing cells can be considered part of a therapeutic approach for either condition and describes his own experiments on spinal cord injury and growing human olfactory mucosa (i.e. tissue from the nasal passages) in the lab. Dr. Robin Franklin, University of Cambridge’s Centre for Brain Repair, focuses on the ability of transplanted olfactory ensheathing cells to keep on creating protective sheaths around the nerve fiber — and the usefulness of that behavior for repairing areas of persistent damage in diseases such as multiple sclerosis. He also discusses why remyelination becomes less efficient with age — an essential question as the potential for transplantation is considered. Using toxin models of CNS demyelination, his research group has been able to identify likely growth factors and cytokine mediators of remyelination.
Tracey DeLucia, a MD/PhD graduate student in Dr. Jones’ laboratory at Loyola University, discusses some of the neurotrophic properties of these ensheathing cells and the mechanisms by which they might work. Included in the discussion of mechanism will be recent studies comparing and contrasting other types of transplanted material and olfactory ensheathing cells and potential molecular effects. Dr. Jones’ group is interested, among other things, in developing combinatorial treatment strategies for complex neurological injury, with particular interest in gonadal steroids as neurotherapeutics to be used in conjunction with olfactory cell transplantation in spinal cord injury transplantation.
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