Acute Putrescine Supplementation with Schwann Cell Implantation Improves Sensory and Serotonergic Axon Growth and Functional Recovery in Spinal Cord Injured Rats

Abstract

Schwann cell (SC) transplantation exhibits 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 a number of experimental SCI models, axonal regeneration is largely limited to local systems and the behavioral improvements are modest without additional combinatory approaches. 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 when implanted subacutely (1 week after injury) into the contused rat spinal cord. Polyamines are ubiquitous organic cations that play an important role in the regulation of the cell cycle, cell division, cytoskeletal organization, and cell differentiation. We show that the combination of putrescine with SCs provides a significant increase in implant size, an enhancement in axonal (sensory and serotonergic) sparing and/or growth, and improved open field locomotion after SCI, as compared to SC implantation alone. These findings demonstrate that polyamine supplementation can augment the effectiveness of SCs when used as a therapeutic approach for subacute SCI repair.

Stem cell transplantation and functional recovery after spinal cord injury: a systematic review and meta-analysis

“…Only 28 articles reported sufficient data to perform a statistical test, including subgroup evaluation ( Fig. 1 ) [ 2 3 4 5 6 7 14 15 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 ]. Besides effect size preparation from these 28 studies, other useful data such as the most popular model, the location of injuries and types of stem cell also extracted from the articles and they are shown in Figs.…”

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

“…Many evidences show that stem cells implants by themselves are not able to stimulate significant numbers of axons to exit the injury site, and provide only modest improvements in functional outcome (Fitch et al, 2008; De Lima et al, 2012). For these reasons, in order to mediate significant anatomical repair and/or functional improvements, the effects of stem cell implants have been increased with various pharmacological, molecular, or biomaterial approaches that overcome intrinsic or extrinsic inhibitors of axon growth, such as neurotrophin supplementation, chondroitinase ABC, polysialic acid, matrix suspension, or cyclic AMP elevation (Fawcett et al, 2006; Pearse et al, 2004 ; Iorgulescu et al, 2015 ; Takami et al, 2002 ; Flora et al, 2013 ). Differently, the present report provides new insights into the effects of transplanted adult neural precursors that likely via local physiologic release of EPO, promote neural tissue sparing and axonal regeneration leading to a significant recovery of function.…”

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials

“…Many preclinical studies using contusion or compression injury models to test the effectiveness of implantation of cells and/or biomolecules, are often delayed one or two weeks after injury, due to the lack of adequate intramedullary space, as well as the hostile nature of the environment in the acutely injured cord [ 33 , 39 , 44 , 45 ], hampering the effectiveness of implant protocols in the clinical setting.…”