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异体脱细胞神经支架联合自体骨髓源干细胞促进轴突再生和髓鞘形成,但不改善神经功能。

Xenogeneic acellular nerve scaffolds supplemented with autologous bone marrow-derived stem cells promote axonal outgrowth and remyelination but not nerve function.

机构信息

Departments of Neurosurgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangdong Province, 510630, Guangzhou, China.

Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Province, 510623, Guangzhou, China.

出版信息

J Biomed Mater Res A. 2018 Dec;106(12):3065-3078. doi: 10.1002/jbm.a.36497. Epub 2018 Sep 7.

DOI:10.1002/jbm.a.36497
PMID:30260554
Abstract

Autologous nerves, artificial scaffolds or acellular nerve scaffolds are commonly used in bridging treatment for peripheral nerve defects. Xenogeneic acellular nerve scaffolds and allogeneic cellular nerve scaffolds have the same structural characteristics. Due to the wider source of raw materials, these latter scaffolds have high-potential value for applications. However, whether their heterogeneity will affect nerve regeneration is unknown. The current study evaluated the efficiency of xenogeneic acellular nerve scaffolds (XANs) combined with 5-ethynyl-2'-deoxyuridine (EdU)-labeling of autologous bone marrow-derived stem cells (BMSCs) for repair of a 1.5 cm gap in rat sciatic nerves. XANs from rabbit tibial nerves were prepared, the structure and components of the scaffolds were evaluated after completely removing the cellular components. Animals were divided into four groups based on graft: the simple XAN group, the XAN + BMSC group, the XAN + Media (from BMSC culture) group, and the autograft group. Serological immune tests showed that XANs induce an immune response in the first 2 weeks after transplantation. Moreover, cell tracking revealed that the proportion of EdU+ cells decreased over time, as shown by the measures at 2 days (70%), 4 days (20%), and 8 days (even <3%) postoperatively. Nerve functional analyses revealed that in contrast to the autograft group results, the XAN-BMSC, XAN + Media, and XAN groups did not exhibit good restoration of the sciatic functional index (SFI) or electrophysiological results (the peak action potential amplitudes) 12 weeks, postoperatively. However, the XAN-BMSC and autograft groups demonstrated greater remyelination and increased axon numbers and myelin thickness than the XAN + Media and XAN groups 12 weeks, postoperatively (p < .05). In conclusion, in the early stage of transplantation, XANs induce a certain degree of inflammation. Although the combination of XANs with autologous BMSCs enhanced the number of regenerated axons and the remyelination, the combination did not effectively improve the recovery of nervous motor function. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3065-3078, 2018.

摘要

自体神经、人工支架或去细胞神经支架常用于周围神经缺损的桥接治疗。异种去细胞神经支架和同种异体细胞神经支架具有相同的结构特征。由于原材料来源更广泛,这些支架具有很高的应用潜力。然而,其异质性是否会影响神经再生尚不清楚。本研究评估了异种去细胞神经支架(XANs)与 EdU 标记的自体骨髓源性干细胞(BMSCs)联合修复大鼠坐骨神经 1.5cm 缺损的效率。制备兔胫神经的 XANs,完全去除细胞成分后评价支架的结构和成分。根据移植物将动物分为四组:单纯 XAN 组、XAN+BMSC 组、XAN+培养基(来自 BMSC 培养)组和自体移植组。血清免疫检测显示,XAN 移植后前 2 周会引起免疫反应。此外,细胞示踪显示,术后 2 天(70%)、4 天(20%)和 8 天(甚至<3%)时 EdU+细胞的比例逐渐减少。神经功能分析显示,与自体移植组结果相比,XAN-BMSC、XAN+培养基和 XAN 组在术后 12 周时坐骨神经功能指数(SFI)或电生理结果(动作电位幅度峰值)均未得到良好恢复。然而,XAN-BMSC 和自体移植组术后 12 周时表现出更大的髓鞘再生,以及更多的轴突数量和髓鞘厚度,而 XAN+培养基和 XAN 组则较少(p<0.05)。总之,在移植的早期阶段,XAN 会引起一定程度的炎症。虽然 XAN 与自体 BMSCs 的联合应用增加了再生轴突的数量和髓鞘再生,但并未有效改善神经运动功能的恢复。©2018Wiley Periodicals, Inc. J Biomed Mater Res Part A:106A:3065-3078,2018。

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