what has to be present for a peripheral nerve to regenerate?
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Nerve regenerative is a complex problem and cell therapy strategies are being developed to enhance axonal regeneration. One approach is to transplant peripheral myelin–forming cells (Schwann cells or olfactory ensheathing cells) that can secrete neurotrophic factors and participate in remyelination of regenerated axons. The objectives of this report are to first review the basic regeneration properties of myelinated axons. Next, to review studies that show functional improvement after transplantation of peripheral myelinating cells in the injured spinal cord. The final objective is to review recent studies using this approach as an adjunct cell therapy for microsurgical repair of peripheral nerve. Methods: Schwann cells and olfactory ensheathing cells were transplanted into injured spinal cord and peripheral nerve. In the microsurgical repair studies, rat sciatic nerves were repaired with epineural sutures (10.0). Olfactory ensheathing cells were transplanted in the experimental group at the time of repair. Histological and behavioral assessment was carried out at 5 weeks postsurgery. Results: Experimental transplantation of olfactory ensheathing cells at the time of microsurgical repair of peripheral nerve leads to increased axonal regeneration across the repair site and improved functional outcome. Conclusions: Olfactory ensheathing cells can integrate and participate in neural repair in both spinal cord and peripheral nerve. They promote axonal sprouting and contribute to remyelination associated with appropriate axon nodal sodium channel clustering necessary for proper impulse conduction. These experimental observations suggest that adjunct cell transplantation with microsurgical repair should be considered as a possible tool in peripheral nerve repair.
Damage to peripheral nerve fibers often results in axonal loss and demyelination followed by regeneration and remyelination under optimal conditions with the possibility of at least some functional recovery. In the central nervous system (CNS), unassisted axonal regeneration is at best rare. Much recent work now indicates that this difference between peripheral nervous system (PNS) and CNS axonal regeneration is the result of both permissive factors present in the PNS and active inhibitory factors present in the CNS. Indeed, knowledge of these differences has encouraged research to develop novel strategies to enhance axonal regeneration. After nerve repair, clinical results are often disappointing and experimental approaches to enhance functional recovery are on their way. These include focal application of neurotrophic factors, blockade of axonal regeneration inhibitory molecules, and cell transplantation. In this article, we review the basic organization of peripheral axons and discuss current experimental strategies using transplantation of peripheral myelin–forming cells to enhance axonal regeneration and remyelination both in the spinal cord and in microsurgical nerve repair.
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