Despite its modest capacity for regeneration, peripheral nervous system injury often results in significant long-term disability. Supplementing peripheral nervous system injury with autologous Schwann cells (SCs) may serve to rejuvenate the postinjury environment to enhance regeneration and ultimately improve functional outcomes. However, human nerve-derived SC (hN-SC) collection procedures require invasive surgical resection. Here, we describe the characterization of SCs from adult human skin (hSk-SCs) of four male donors ranging between 27 and 46 years old. Within five weeks of isolating and culturing adherent mixed skin cells, we were able to obtain 3–5 million purified SCs. We found that hSk-SCs appeared transcriptionally indistinguishable from hN-SCs with both populations exhibiting expression of SC genes including: SOX10, SOX9, AP2A1, CDH19, EGR1, ETV5, PAX3, SOX2, CX32, DHH, NECL4, NFATC4, POU3F1, S100B, and YY1. Phenotypic analysis of hSk-SCs and hN-SCs cultures revealed highly enriched populations of SCs indicated by the high percentage of NES+ve, SOX10+ve, s100+ve and p75+ve cells, as well as the expression of a battery of other SC-associated proteins (PAX3, CDH19, ETV5, SOX2, POU3F1, S100B, EGR2, and YY1). We further show that both hSk-SCs and hN-SCs are capable of promoting axonal growth to similar degrees and that a subset of both associate with regenerating axons and form myelin following transplantation into the injured mouse sciatic nerve. Interestingly, although the majority of both hSk-SCs and hN-SCs maintained SOX10 immunoreactivity following transplant, only a subset of each activated the promyelinating factor, POU3F1, and were able to myelinate. Taken together, we demonstrate that adult hSk-SCs are genetically and phenotypically indistinguishable to hN-SCs.

Object: This study evaluated a chitosan tube for regeneration of the injured peripheral nerve in a rodent transected sciatic nerve model in comparison to autologous nerve graft repair. Methods: Chitosan hollow tube was used to bridge a 10-mm gap between the proximal and distal ends in 11 rats. In the control group, an end-to-end coaptation of 10-mm long autologous nerve graft was performed in 10 rats for nerve reconstruction. Results: SFI showed an insignificant advantage to the autologous group both at 30 days (P 5 0.177) and at 90 days post procedure (P 5 0.486). Somato-sensory evoked potentials (SSEP) and compound muscle action potentials (CMAP) tests showed similar results between chitosan tube (group 1) and autologous (group 2) groups with no statistically significant differences. Both groups presented the same pattern of recovery with 45% in group 1 and 44% in group 2 (P 5 0.96) showing SSEP activity at 30 days. At 90 days most rats showed SSEP activity (91% vs.80% respectively, P 5 0.46). The CMAP also demonstrated no statistically significant dif-ferences in latency (1.39 ms in group 1 vs. 1.63 ms in group 2; P 5 0.48) and amplitude (6.28 mv vs. 6.43 mv respectively; P 5 0.8). Ultra-sonography demonstrated tissue growth inside the chitosan tube. Gastrocnemius muscle weight showed no statistically significant difference. Histomorphometry of the distal sciatic nerve, 90 days post reconstructive procedure, showed similar number of myelinated fibers and size parameters in both groups (P _0.05). Conclusions: Chitosan hollow tube used for peripheral nerve reconstruction of rat sciatic nerve showed similar results in comparison to autologous nerve grafting. V C 00:000-000, 2015.

Skin-derived precursor Schwann cell (SKPSC) therapy has been identified as a potentially beneficial treatment for peripheral nerve injuries. One hypothesised mechanism by which SKPSCs enhance recovery is via the modulation of macrophages. In the present study, we investigated the immunomodulatory properties of adult rat SKPSCs, and demonstrated that these cells expressed a battery of cytokines, including interferon-γ (IFN-γ), interleukin (IL)-1β, and, most abundantly, IL-6. Whereas macrophages exposed to depleted or fibroblast-conditioned medium secreted minimal amounts of tumor necrosis factor-α (TNF-α), in the presence of SKPSC-conditioned medium, macrophages secreted > 500 pg/mL TNF-α. Following the transplantation of SKPSCs into injured rat sciatic nerves, we observed an SKPSC density-dependent increase in the number of macrophages (Pearson's r = 0.66) and an SKPSC density-dependent decrease in myelin debris (Pearson's r = -0.68). To determine the effect of IL-6 in a proinflammatory context, macrophage cultures were primed with either lipopolysaccharide (LPS)/IFN-γ/IL-1β or LPS/IFN-γ/IL-1β + IL-6, and this showed a 212% and 301% increase in the number of inducible nitric oxide synthase (iNOS)-positive proinflammatory macrophages respectively. In contrast to neurons exposed to conditioned medium from unprimed macrophages, neurons treated with conditioned medium from proinflammatory-primed macrophages showed a 13-26% reduction in neurite outgrowth. Anti-IL-6 antibody combined with SKPSC transplant therapy following nerve injury did not alter macrophage numbers or debris clearance, but instead reduced iNOS expression as compared with SKPSC + IgG-treated rats. SKPSC + anti-IL-6 treatment also resulted in a two-fold increase in gastrocnemius compound muscle action potential amplitudes as compared with SKPSC + IgG treatment. Understanding the mechanisms underlying immunomodulatory aspects of SKPSC therapy and developing approaches to manipulate these responses are important for advancing Schwann cell-based therapies.

The present study and our previous investigations showed that the laser phototherapy increases biochemical activity and improves morphological recovery in muscle and, thus, could have direct therapeutic applications on muscle, especially during progressive atrophy resulting from PNI.