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
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