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  • Schwann Cell(SC) Transplantation for Spinal Cord Injury in Mini Pigs: A Preliminary Report

    Final Number:
    1221

    Authors:
    Howard B. Levene MD PhD; Juan Pablo Solano MD; Francisco Benavides MD; Gagani Athauda; Kyle Padgett PhD; Allan D. Levi MD, PhD, FACS; Dalton Dietrich PhD; James D. Guest MD, PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Rodent research suggests introduction of myelin producing cells may restore function to demyelinated axons spared from initial injury. It is important to test therapies in large animal models.

    Methods: Yucatan Mini-Pigs (~15-20 kg) were used. A Thoracic7 pneumatic contusion (4mm depth, 150msec, 30 psi) was created. The animals were imaged post-injury (4.7 T MRI). MEPs/SSEPs/cord potentials were recorded. Assessed were ambulation, neurological scales, &histology. Categories: 1)Uninjured animals: (a) no treatment, (b) needle insertion, (c) media injection. 2) Injured animals: (a) no treatment, (b) needle insertion, (c) media injection. 3) injured animals w/injections of (a)50 (b)100,(c)150 uL over several minutes (200,000 SC/uL). Injections were performed at 2-3 weeks post-injury into the injury epicenter (3.5 mm depth). Initial transplantations used allograft SC. Subsequent animals received autologous SC . Animals were euthanized at 2 days or 2-3 weeks post-transplantation. MRIs were performed on explanted spinal cord (injury quantification). Histology assessed injection injury, cell survival, biodistribution, inflammatory responses, &injury morphology.

    Results: 38 pigs have undergone injury. Large injections (100, 150 ul) produced transient locomotor functional loss; smaller injections (50ul) did not thus far. In pigs with preserved MEPs/SSEPs after injury, large injections resulted in conduction loss/alteration. On MRI large injections were associated with gray matter tissue dissection. Histological analysis showed contusions lead to tissue cavitation similar to humans. Allografted SC were rejected. Preliminary autograft data indicated cell survival.

    Conclusions: Transplantation of SC into spinal cord injured pigs appears to be safe and well tolerated at preliminary phases of testing. Further data is expected to refine the technique of cell delivery. The data is expected to address safety/efficacy issues of SC transplantation as a prelude to future human clinical trials.

    Patient Care: Our research aims to provide a new therapy for treating patients with Spinal Cord Injury. As this technique is developed and proven safe, it will serve as a prelude to future human clniical trials.

    Learning Objectives: by the conclusion of the session, participants should be able to 1) Describe the importance of using autologous cells in Spinal Cord Injury treatment 2) Discuss, in small groups, the techniques and challenges in delivering this therapy safely and 3) identify aspects of this treatment as an effective method of treating Spinal Cord Injury

    References: Akiyama, Y., C. Radtke, et al. (2002). "Remyelination of the spinal cord following intravenous delivery of bone marrow cells." Glia 39(3): 229-36. Andrews, M. R. and D. J. Stelzner (2007). "Evaluation of olfactory ensheathing and schwann cells after implantation into a dorsal injury of adult rat spinal cord." J Neurotrauma 24(11): 1773-92. Black, J. A., S. G. Waxman, et al. (2006). "Remyelination of dorsal column axons by endogenous Schwann cells restores the normal pattern of Nav1.6 and Kv1.2 at nodes of Ranvier." Brain 129(Pt 5): 1319-29. Guest, J. D., A. Rao, et al. (1997). "The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord." Exp Neurol 148(2): 502-22. Pearse, D. D., F. C. Pereira, et al. (2004). "cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury." Nat Med 10(6): 610-6. Pearse, D. D., A. R. Sanchez, et al. (2007). "Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: Survival, migration, axon association, and functional recovery." Glia 55(9): 976-1000.

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