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在大鼠模型中,纤维蛋白基质中的脂肪干细胞可增强神经外膜缝合后的神经再生。

ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model.

作者信息

Reichenberger Matthias A, Mueller Wolf, Hartmann Jennifer, Diehm Yannick, Lass Ulrike, Koellensperger Eva, Leimer Uwe, Germann Günter, Fischer Sebastian

机构信息

ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.

University Hospital Leipzig, Department of Neuropathology, University of Leipzig, Leipzig, Germany.

出版信息

Microsurgery. 2016 Sep;36(6):491-500. doi: 10.1002/micr.30018. Epub 2015 Dec 30.

DOI:10.1002/micr.30018
PMID:26716599
Abstract

BACKGROUND

Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin-glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model.

MATERIALS AND METHODS

Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re-suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N- and G-ratios. Additionally, muscle weight quotient (operated vs. non-operated site of the same animal) was calculated and compared between treatment and control groups. For co-detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM-DiI, SMA, and S-100 antibodies, respectively.

RESULTS

ADSCs led to a significant increase of myelinization at day 21 (0.508 ± 0.085 μm vs. 0.381 ± 0.044 μm, P = 0.025) and day 35 (0.872 ± 0.09 µm vs. 0.495 ± 0.078 µm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 ± 119 vs. 129 ± 63; P = 0.003) and day 63 (284 ± 137 vs. 111 ± 26; P = 0.046) after surgery. N- and G-ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P < 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% ± 6.16% vs. 35.03% ± 2.61%; P = 0.014) and day 63 (65.49% ± 2.81% vs. 58.79% ± 4.06%; P = 0.009) after surgery. Co-detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis.

CONCLUSION

ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation. © 2015 Wiley Periodicals, Inc. Microsurgery 36:491-500, 2016.

摘要

背景

由于其独特的特性,脂肪来源干细胞(ADSCs)在促进神经再生方面具有广阔的应用前景。本研究旨在探讨在大鼠坐骨神经模型中,纤维蛋白胶包埋的ADSCs是否是一期神经吻合的有益辅助手段。

材料与方法

50只雄性Lewis大鼠接受坐骨神经横断及随后的神经外膜缝合修复。治疗组接受重悬于纤维蛋白胶中的ADSCs,而对照组仅接受纤维蛋白胶。在术后7天、21天、35天和63天,分析内容包括轴突计数、髓鞘厚度以及N-和G-比值。此外,计算并比较治疗组和对照组之间的肌肉重量商(同一动物手术侧与非手术侧相比)。为了共同检测存活的ADSCs、血管壁和雪旺细胞,分别用CM-DiI、平滑肌肌动蛋白(SMA)和S-100抗体进行免疫标记。

结果

术后第21天(0.508±0.085μm对0.381±0.044μm,P = 0.025)和第35天(0.872±0.09μm对0.495±0.078μm;P = 0.01),ADSCs导致髓鞘形成显著增加。术后第21天(420±119对129±63;P = 0.003)和第63天(284±137对111±26;P = 0.046),轴突计数显著增加。与对照组相比,N-和G-比值在各时间点均有显著差异,表明ADSC治疗可促进神经再生(P < 0.05)。术后第21天(44.01%±6.16%对35.03%±2.61%;P = 0.014)和第63天(65.49%±2.81%对58.79%±4.06%;P = 0.009),治疗组的肌肉重量商显著高于对照组。免疫标记细胞的共同检测显示,在神经修复部位及神经元内血管附近存在存活的ADSCs,表明ADSCs积极参与神经再生和相关血管生成过程。

结论

纤维蛋白基质包埋的ADSCs可显著促进一期神经吻合后周围神经损伤的再生。© 2015威利期刊公司。显微外科学36:491 - 500,2016年。

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