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静脉移植物内的施万样间充质干细胞促进面神经再生和髓鞘形成。

Schwann-like mesenchymal stem cells within vein graft facilitate facial nerve regeneration and remyelination.

机构信息

The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.

出版信息

Brain Res. 2011 Apr 6;1383:71-80. doi: 10.1016/j.brainres.2011.01.098. Epub 2011 Feb 3.

Abstract

To compare the ability of bone marrow mesenchymal stem cells (MSCs) and transdifferentiated Schwann-like MSCs (tMSCs) in promoting transected facial nerve branches repair in a rabbit model of injury, rabbit tMSCs were induced from bone marrow MSCs, and Schwann cells markers were assessed by Western blot analysis. The left facial nerve buccal branch was transected to form a 1-cm gap in 54 rabbits, and the gaps were immediately bridged using autologous vein grafts. Animals were then randomly assigned to three groups: vein graft (VG); VG+MSCs, and VG+tMSCs (n=18/group). Saline, autologous MSCs, and Schwann-like tMSCs were injected into vein conduits. Rabbits were sacrificed at week 4, 8, and 16 post-surgery. Facial nerves regeneration and myelination were analyzed by functional, immunohistochemical, and morphological tests. In addition, myelin protein genes expression, including peripheral myelin protein 22 (PMP22), myelin protein zero (P0), and myelin basic protein (MBP), in transplanted cells in vivo were assayed using real time quantitative-reverse transcription-polymerase chain reaction (RT-PCR). Rabbit tMSCs expressed Schwann cells markers, and results demonstrated better facial nerve functional recovery in the VG+tMSCs group, with earlier horseradish peroxidase (HRP) positive neurons appearance and a greater number of MBP positive myelinated axons since 4weeks after transplantation. Moreover, RT-PCR analysis showed transplanted tMSCs in vivo expressed higher myelin proteins at mRNA level than those of MSCs during the first 8weeks of neural regeneration. This study suggests that rabbit transdifferentiated Schwann-like MSCs within autogenous vein graft accelerate transected axons regeneration and achieve better remyelinization.

摘要

为了比较骨髓间充质干细胞(MSCs)和诱导分化的雪旺样细胞(tMSCs)在促进兔面神经损伤模型中面神经分支修复中的能力,我们从骨髓 MSCs 中诱导产生兔 tMSCs,并通过 Western blot 分析评估雪旺细胞标志物。在 54 只兔子中,将左侧面神经颊支切断形成 1cm 的间隙,并用自体静脉移植物立即桥接。然后,动物被随机分为三组:静脉移植物(VG);VG+MSCs 和 VG+tMSCs(每组 n=18)。将生理盐水、自体 MSCs 和诱导分化的雪旺样 tMSCs 注入静脉导管。手术后第 4、8 和 16 周处死兔子。通过功能、免疫组织化学和形态学测试分析面神经再生和髓鞘形成。此外,还使用实时定量逆转录-聚合酶链反应(RT-PCR)检测体内移植细胞中髓鞘蛋白基因表达,包括周围髓鞘蛋白 22(PMP22)、髓鞘蛋白零(P0)和髓鞘碱性蛋白(MBP)。兔 tMSCs 表达雪旺细胞标志物,结果表明 VG+tMSCs 组面神经功能恢复更好,自移植后 4 周起 HRP 阳性神经元出现更早,MBP 阳性有髓轴突数量更多。此外,RT-PCR 分析显示,在神经再生的前 8 周内,体内移植的 tMSCs 在 mRNA 水平上表达更高的髓鞘蛋白。本研究表明,兔自体静脉移植物内诱导分化的雪旺样细胞可加速切断轴突的再生,并实现更好的髓鞘化。

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