Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. Brain Res

Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
Brain research (Impact Factor: 2.84). 12/2008; 1254(13):10-7. DOI: 10.1016/j.brainres.2008.11.036
Source: PubMed


While axonal regeneration is more successful in peripheral nerve than in the central nervous system, it is by no means complete and research to enhance peripheral nerve regeneration is clinically important. Olfactory ensheathing cells (OECs) are known to enhance axonal regeneration and to produce myelin after transplantation. In contrast to Schwann cells their migratory potential and ability to penetrate glial scars is higher. This study evaluated the effect of OEC transplantation on microsurgically repaired sciatic nerves. Rat sciatic nerves were transected followed by microsurgical repair and transplantation of OECs or injection of medium without cells. Twenty-one days later the nerves were removed and prepared for either histology or electrophysiological analysis. Footprint analysis was carried out at 7, 14 and 21 days. The OECs survived and integrated into the repaired nerves as indicated by eGFP-expressing cells aligned with neurofilament identified axons bridging the repair site. Moreover, regenerated axons were myelinated by the transplanted OECs and nodes of Ranvier were formed. Conduction velocity in the OEC transplant group was increased in comparison to the microsurgical repair alone, and improved stepping was observed in the transplant group. These results suggest that presentation of OECs at the time of nerve injury enhances regeneration and improves functional outcome. Even a modest improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

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    • "Due to these catastrophic consequences, many studies have investigated the regeneration of peripheral nerves (Navarro et al., 2007). Several techniques have been confirmed useful in improving PNI, including the administration of neurotrophic factors (Raivich et al., 1991; Yin et al., 2001; Oya et al., 2002; Pierson et al., 2002), the blockade of axonal regeneration inhibitory molecules (Deumens et al., 2006; Radtke et al., 2009), stem cells (Cuevas et al., 2002; Uemura et al., 2012), and the use of nerve conduits (Weber et al., 2000; Taras et al., 2011). Fibrosis is also an important issue in patients with PNI, and many methods, such as low-dose external radiation (Petersen et al., 1996; Görgülü et al., 2003) and agents that are immunosuppressive (Wang et al., 1997; Lee et al., 2000; Ozgenel, 2003; Ozay et al., 2007) have been applied in this context. "
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    ABSTRACT: Glioblastoma cyst fluid contains growth factors and extracellular matrix proteins which are known as neurotrophic and neurite-promoting agents. Therefore, we hypothesized that glioblastoma cyst fluid can promote the regeneration of injured peripheral nerves. To validate this hypothesis, we transected rat sciatic nerve, performed epineural anastomosis, and wrapped the injured sciatic nerve with glioblastoma cyst fluid-or saline-soaked gelatin sponges. Neurological function and histomorphological examinations showed that compared with the rats receiving local saline treatment, those receiving local glioblastoma cyst fluid treatment had better sciatic nerve function, fewer scars, greater axon area, counts and diameter as well as fiber diameter. These findings suggest that glioblastoma cyst fluid can promote the regeneration of injured sciatic nerve and has the potential for future clinical application in patients with peripheral nerve injury. © 2015, Editorial Board of Neural Regeneration Research. All rights reserved.
    Full-text · Article · Oct 2015 · Neural Regeneration Research
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    • "The rationale is that the transplanted MSCs provide neuroprotection, neovascularisation , and induction of axonal sprouting by their production of cytokines and neurotrophic factors [6]. Peripheral myelinforming cells (Schwann cells and olfactory ensheathing cells) have been shown to improve survival when directly transplanted into peripheral nerve and lead to improvement in functional outcome [7] [8] [9]. However, harvesting of these cells requires nerve biopsy in the case of Schwann cells and biopsy from nasal mucosa both of which have some potential morbidity associated with them. "
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    ABSTRACT: Peripheral nerve injury is a common and devastating complication after trauma and can cause irreversible impairment or even complete functional loss of the affected limb. While peripheral nerve repair results in some axonal regeneration and functional recovery, the clinical outcome is not optimal and research continues to optimize functional recovery after nerve repair. Cell transplantation approaches are being used experimentally to enhance regeneration. Intravenous infusion of mesenchymal stromal cells (MSCs) into spinal cord injury and stroke was shown to improve functional outcome. However, the repair potential of intravenously transplanted MSCs in peripheral nerve injury has not been addressed yet. Here we describe the impact of intravenously infused MSCs on functional outcome in a peripheral nerve injury model. Rat sciatic nerves were transected followed, by intravenous MSCs transplantation. Footprint analysis was carried out and 21 days after transplantation, the nerves were removed for histology. Labelled MSCs were found in the sciatic nerve lesion site after intravenous injection and regeneration was improved. Intravenously infused MSCs after acute peripheral nerve target the lesion site and survive within the nerve and the MSC treated group showed greater functional improvement. The results of study suggest that nerve repair with cell transplantation could lead to greater functional outcome.
    Full-text · Article · Dec 2013
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    • "Although BC bridging lead to almost comparable regeneration results to NT, there is still optimization potential. Since transplantation of axon growth-supporting cells is known to enhance peripheral nerve regeneration [Galla et al., 2004; Hood et al., 2009; Radtke et al., 2009a, 2011], the presented study evaluated whether the intraluminal addition of OEC and SC potentiated axonal regeneration. The cell-filled BCs remained identifiable at 16 weeks survival time resembling a normal epineurial layer. "
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    ABSTRACT: The aim of this study was to evaluate long-term regenerative capacity over a 15-mm nerve gap of an autologous nerve conduit, the biogenic conduit (BC), 16 weeks after sciatic nerve transection in the rat. A 19-mm long polyvinyl chloride (PVC) tube was implanted parallely to the sciatic nerve. After implantation, a connective tissue cover developed around the PVC-tube, the so-called BC. After removal of the PVC-tube the BCs filled with fibrin (n = 8) were compared to autologous nerve grafts (n = 8). Sciatic functional index (SFI) was evaluated every 4 weeks, histological evaluation was performed at 16 weeks postimplantation. Regenerating axons were visualized by retrograde labelling. SFI revealed no significant differences. Nerve area and axon number in the BC group were significantly lower than in the autologous nerve group (P < 0.05; P < 0.01). Analysis of myelin formation showed no significant difference in both groups. Analysis of N-ratio revealed lower values in the BC group (P < 0.001). This study reveals the suitability of BC for nerve gap bridging over a period of 16 weeks with functional recovery to comparable extent as the autologous nerve graft despite impaired histomorphometric parameters.
    Full-text · Article · Jul 2012 · Microsurgery
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