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Development of Combination Strategies to Repair the Injured Spinal Cord
The goal in my laboratory has been to foster regeneration of axons across and beyond the area of spinal cord injury (SCI) since coming to The Miami Project.
To improve axon regeneration after SCI, we have investigated Schwann cell transplantation in combination with a steroid, increases in cyclic AMP levels, lessening formation of proteoglycans (molecules that inhibit axon growth), olfactory ensheathing cell transplantation, and provision of neurotrophic factors in various ways (including genetically modifying Schwann cells to improve their neurotrophic factor secretory capability). Both complete spinal cord transection and contusion models have been utilized. We are studying gene differences between neurons that are able to regrow onto a Schwann cell bridge placed in the area of injury and those that do not grow onto the bridge. Currently we are testing ways in which to modify the spinal cord-Schwann cell implant interfaces for improved permissivity for axons to enter and exit the implant and clinically relevant biomaterials and conduits in which to transplant Schwann cells for improved survival and alignment.
A contribution of my laboratory has been to introduce the novel use of a Schwann cell bridge across a complete transection gap in the adult rat spinal cord to be able to identify regenerated axons. The combination strategies we have evaluated have improved outcome consistently in both lesion models compared to Schwann cell transplantation alone. For example, when neurotrophins are introduced along with Schwann cells, there are far more regrowing fibers and an increased variety of fibers in the implant, including those from distant neuronal somata positioned in the brainstem. That combination strategies are more effective than Schwann cell implantation alone is undoubtedly, at least in part, due to the many and varied reactions of the spinal cord tissue to injury.
The goal in my laboratory has been to foster regeneration of axons across and beyond the area of spinal cord injury (SCI) since coming to The Miami Project.
To improve axon regeneration after SCI, we have investigated Schwann cell transplantation in combination with a steroid, increases in cyclic AMP levels, lessening formation of proteoglycans (molecules that inhibit axon growth), olfactory ensheathing cell transplantation, and provision of neurotrophic factors in various ways (including genetically modifying Schwann cells to improve their neurotrophic factor secretory capability). Both complete spinal cord transection and contusion models have been utilized. We are studying gene differences between neurons that are able to regrow onto a Schwann cell bridge placed in the area of injury and those that do not grow onto the bridge. Currently we are testing ways in which to modify the spinal cord-Schwann cell implant interfaces for improved permissivity for axons to enter and exit the implant and clinically relevant biomaterials and conduits in which to transplant Schwann cells for improved survival and alignment.
A contribution of my laboratory has been to introduce the novel use of a Schwann cell bridge across a complete transection gap in the adult rat spinal cord to be able to identify regenerated axons. The combination strategies we have evaluated have improved outcome consistently in both lesion models compared to Schwann cell transplantation alone. For example, when neurotrophins are introduced along with Schwann cells, there are far more regrowing fibers and an increased variety of fibers in the implant, including those from distant neuronal somata positioned in the brainstem. That combination strategies are more effective than Schwann cell implantation alone is undoubtedly, at least in part, due to the many and varied reactions of the spinal cord tissue to injury.
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Aisha Khan,Anthony Diaz,Adriana E Brooks,S Shelby Burks,Gagani Athauda, Patrick Wood,Yee-Shuan Lee,Risset Silvera, Maxwell Donaldson, Yelena Pressman, Kim D Anderson,Mary Bartlett Bunge,
Journal of neurosurgery. Spineno. 1 (2021): 135-144
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