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Transplantation of Preconditioned Schwann Cells in Peripheral Nerve Grafts After Contusion in the Adult Spinal CordImprovement of Recovery in a Rat Model
Alexandre Rasouli, MD1; Nitin Bhatia, MD1; Sourabh Suryadevara, BS1; Kim Cahill, BS1; Ranjan Gupta, MD1
1 University of California, Irvine, 2226 Gillespie Neuroscience Research Facility, Irvine, CA 92697. E-mail address for R. Gupta: ranjang@uci.edu
View Disclosures and Other Information
In support of their research for or preparation of this manuscript, R. Gupta received grants or outside funding from the National Institute of Neurological Disorders and Stroke (NS02221 and NS049203) and the Roman Reed Foundation. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the University of California, Irvine, California

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2006 Nov 01;88(11):2400-2410. doi: 10.2106/JBJS.E.01424
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Abstract

Background: Recovery after injury to the peripheral nervous system is based on the pro-regenerative relationship between axons and the extracellular matrix, a relationship established by Schwann cells. As mechanical conditioning of Schwann cells has been shown to stimulate their regenerative behavior, we sought to determine whether transplantation of these cells to the central nervous system (i.e., the spinal cord), with its limited regenerative capacity after injury, would improve axonal regeneration and functional recovery.

Methods: A moderate contusion injury of the spinal cord was created with a force-directed impactor in forty-eight adult Sprague-Dawley rats, and, at one week postinjury, the spinal cords were reexposed in all animals. In twenty-four of these animals, peripheral nerve grafts with Schwann cells that had been obtained from the sciatic nerves of donor animals, and had been either untreated or subjected to mechanical conditioning, were transplanted to the contused area of the cords following resection of the glial scar. Another group of animals was treated with glial scar excision only, and a fourth group had the contusion injury but neither glial excision nor transplantation. Scores according to the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale were assigned preoperatively and weekly thereafter. Tract tracing of descending and ascending spinal cord tracts was performed at six weeks postoperatively for quantitative histological evaluation of axonal regeneration.

Results: While the recovery following glial scar excision without peripheral nerve transplantation was significantly worse than the recovery in the other groups, both transplantation groups had significantly higher BBB scores than the controls (no transplantation) in the early postoperative period (p < 0.05). Moreover, histological analysis showed markedly increased axonal regeneration at the lesional sites in the animals treated with the mechanically conditioned grafts than in the other groups (p < 0.05).

Conclusions: Functional recovery after spinal cord contusion improved following glial scar excision with transplantation of Schwann cells in peripheral nerve grafts to the contusion areas. Although recovery did not differ significantly between the transplantation groups, only the preconditioned grafts led to axonal regeneration at and past the lesional site. These grafts may further enhance functional recovery as the descending tracts eventually reach their target end-organs.

Clinical Relevance: Transplantation of Schwann cells in peripheral nerve grafts significantly improved functional and axonal recovery following a contusion spinal cord injury in rats and warrants further investigation for potential clinical applications.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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