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 sub-acute and chronic human SCI. Although SC implants provide a receptive environment for axonal re-growth 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 min or 1 week after SCI, could enhance the efficacy of SCs sub-acutely (1 week post-injury) 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 to 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 100um and 500um 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 (i.e. superior hind paw placement and tail positioning, and fewer footfalls on a gridwalk) throughout the 10 wks post-SCI.
Conclusions: 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 sub-acute SCI repair.
Patient Care: To date no treatment can significantly reverse the tragic debilitation associated with SCI. Schwann cell transplantation displays great promise and is now under investigation in clinical trials, however remains limited by an inability to coax axonal regeneration not just through the injury site, but far beyond. As such, adjunctive therapies are crucial to complementing SC transplantation. Our results show that supplementation with polyamines markedly improves histologic and functional outcomes in SCI.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the challenges facing spinal cord injury therapies, 2) Describe the successes of Schwann cell transplantation for SCI, 3) Discuss the benefits of supplementing Schwann cell implantation with polyamine administration.
References: Flora et al. Combining neurotrophin-transduced schwann cells and rolipram to promote functional recovery from subacute spinal cord injury. Cell Transplant. 2013;22(12):2203-17.
Kanno et al. Schwann cell transplantation for spinal cord injury repair: its significant therapeutic potential and prospectus. Rev Neurosci. 2015 Jan 10.