BACKGROUND Emerging evidence suggests that neural crest-derived cells (NCCs) present important functions in peripheral nerve regeneration to correct the insufficiency of autogenous Schwann cells. Postmigratory NCCs have been successfully isolated from adult rat bone marrow in our previous work. In this study, we aim to provide neural crest-derived Schwann cell precursors (SCPs) for repair of nerve defects in adult rats, and partially reveal the mechanisms involved in neuroregeneration of cell therapy. METHODS A clonal cell line of neural crest precursors of rat bone marrow origin (rBM-NCPs) with SCP identity was expanded in adherent monolayer culture to ensure the stable cell viability of NCPs and potentiate the repair of nerve defects after rBM-NCPs implantation based on tissue engineering nerve grafts (TENG). Here the behavioral, morphological, and electrophysiological detection was performed to evaluate the therapy efficacy. We further investigated the treatment with NCP-conditioned medium (NCP-CM) to sensory neurons after exposure to oxygen-glucose-deprivation (OGD) and partially compared the expression of trophic factor genes in rBM-NCPs with that in mesenchymal stem cells of bone marrow origin (rBM-MSCs). RESULTS It was showed that the constructed TENG with rBM-NCPs loaded into silk fibroin fiber scaffolds/chitosan conduits repaired 10-mm long sciatic nerve defects more efficiently than conduits alone. The axonal regrowth, remyelination promoted the reinnervation of the denervated hind limb muscle and skin and thereby alleviated muscle atrophy and facilitated the rehabilitation of motor and sensory function. Moreover, it was demonstrated that treatment with NCP-CM could restore the cultured primary sensory neurons after OGD through trophic factors including epidermal growth factor (EGF), platelet-derived growth factor alpha (PDGFα), ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor alpha (VEGFα). CONCLUSIONS In summary, our findings indicated that monolayer-cultured rBM-NCPs cell-based therapy might effectively repair peripheral nerve defects partially through secreted trophic factors, which represented the secretome of rBM-NCPs differing from that of rBM-MSCs.

中文翻译：

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骨髓来源的神经rest前体部分通过分泌的营养因子改善神经缺损的修复。

背景技术越来越多的证据表明，神经c源性细胞（NCC）在周围神经再生中具有重要的功能，以纠正自体雪旺细胞的功能不足。在我们以前的工作中，已经成功地从成年大鼠骨髓中分离出了迁徙后的NCC。在这项研究中，我们旨在提供神经c衍生的雪旺氏细胞前体（SCPs）修复成年大鼠的神经缺损，并部分揭示参与细胞疗法神经再生的机制。方法在贴壁单层培养中扩增具有SCP身份的大鼠骨髓起源神经precursor前体（rBM-NCPs）的克隆细胞系，以确保NCPs稳定的细胞存活力，并在基于rBM-NCPs植入后增强神经缺损的修复。组织工程神经移植（TENG）。这里是行为的，形态的 并进行电生理检测以评价疗效。我们进一步研究了使用NCP条件培养基（NCP-CM）对暴露于缺氧-葡萄糖剥夺（OGD）后的感觉神经元的处理，并部分比较了营养因子基因在rBM-NCPs和骨骼间充质干细胞中的表达骨髓起源（rBM-MSC）。结果表明，将rBM-NCPs装载到丝素蛋白纤维支架/壳聚糖导管中的TENG比单独的导管能更有效地修复10 mm长的坐骨神经缺损。轴突再生，髓鞘再生促进了失神经的后肢肌肉和皮肤的神经支配，从而减轻了肌肉的萎缩，并促进了运动和感觉功能的恢复。而且，研究表明，NCP-CM处理可通过营养因子（包括表皮生长因子（EGF），血小板衍生生长因子α（PDGFα），睫状神经营养因子（CNTF）和血管内皮生长）恢复OGD后培养的初级感觉神经元。因子α（VEGFα）。结论总之，我们的研究结果表明，单层培养的基于rBM-NCPs的细胞疗法可能部分地通过分泌的营养因子有效地修复了周围神经缺损，这代表了rBM-NCPs的分泌组不同于rBM-MSC的分泌组。