182 Acute Putrescine Supplementation With Schwann Cell Transplantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injury. (August 2015) - Lorgulescu, Bryan
Abstract : INTRODUCTION: Schwann cell (SC) transplantation demonstrates significant potential for spinal cord injury (SCI) repair and its use as a therapeutic modality has now progressed to clinical trials for subacute and chronic human SCI. Although SC implants provide a receptive environment for axonal regrowth and support functional recovery in various SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without adjunctive therapies. METHODS: In the current study we investigated whether the concurrent delivery of the polyamine putrescine, started either 30 minutes or 1 week after SCI, could enhance the efficacy of SCs subacutely (1 week postinjury) implanted into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. RESULTS: We show that the combination of SC implantation with putrescine supplementation for SCI, when compared with SC implant + vector controls, significantly increased implant size (1.8-fold increase in implant area, P < .05), enhanced serotonergic axon sparing and growth (4.5- and 1.5-fold more 5HT+ fibers at 100 μm and 500 μm rostral to the implant epicenter, respectively, P < .01), stimulated sensory axon growth into the implant epicenter (3.9-fold more CGRP+ fibers, P < .001), and improved locomotor functional recovery (ie, superior hind paw placement and tail positioning, and fewer footfalls on a gridwalk) throughout the 10 weeks post-SCI. CONCLUSION: These findings demonstrate that polyamine supplementation, particularly in the acute setting following SCI, can augment the effectiveness of SC transplantation when used as a combined therapeutic approach for subacute SCI repair.