Transplantation of adipose-derived stem cells for peripheral nerve repair

Transplantation of adipose-derived stem cells for peripheral nerve repair
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DOI:
10.3892/ijmm.2011.725
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发表时间:
2011-10-01
影响因子:
5.4
通讯作者:
Tong, Xiaojie
Tong, Xiaojie
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Guibo;Cheng, Yongxia;Tong, Xiaojie

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骨髓间充质干细胞已成为神经组织工程中一个非常有吸引力的细胞移植来源。理想的移植干细胞应易于获得,并应在体外快速增殖,具有低免疫原性。本研究旨在探讨脂肪干细胞(ADSC)在周围神经修复中的再生潜能。从大鼠脂肪组织中分离ADSCs,培养至贴壁细胞形态均一,呈成纤维细胞样,与脱细胞神经同种异体移植物(ANAs)一起移植到大鼠坐骨神经横断缺损10 mm的模型中。细胞移植后,我们发现ADSC植入促进了运动行为的功能恢复,并增加了胫前肌的湿重比。在电生理测试中,我们发现ADSC植入动物中激活纤维的百分比较高,神经传导速度和振幅的增加证明了这一点。组织学检查显示,与对照组相比,ADSC植入动物的神经纤维数量、轴突直径和髓鞘厚度显著增加。此外,我们证明了ADSC植入后再生过程的进展伴随着早期和晚期神经营养因子表达的升高。这些结果表明,ADSC可以促进周围神经损伤的修复,ADSC与ANA联合移植是治疗远距离周围神经缺损的一种新方法。我们的数据还提供了证据表明神经营养因子的产生与植入的ADSC的再生潜力密切相关。
Mesenchymal stem cells have become a very attractive source of cell implantation for neural tissue engineering. The ideal stem cells for transplantation should be easily obtained, and should rapidly proliferate in vitro and have low immunogenicity. The purpose of this study was to investigate the regenerative potential of adipose-derived stem cells (ADSC) on peripheral nerve repair. ADSCs were isolated from rat adipose tissue and cultured until adherent cells became morphologically homogeneous with a fibroblast-like shape, and transplanted with acellular nerve allografts (ANAs) into rat models with a 10 mm gap of transected sciatic nerve defect. After cell transplantation, we found that ADSC implantation improved functional recovery of exercise behavior and increased wet weight ratio of the anterior tibial muscle. In the electrophysiological testing, we found that the percentage of activated fibers was higher in the ADSC-implanted animals as evidenced by the increase of nerve conduction velocity and amplitude. Histological examination revealed that the number of nerve fibers, axonal diameter and myelin thickness were significantly higher in the ADSC-implanted animals compared to the control. In addition, we demonstrated that the progression of the regenerative process after ADSC implantation was accompanied by elevated expression of neurotrophic factors at both the early and later phase. Taken together, these results suggest that ADSCs can promote the repair of peripheral nerve injury, and the combination of ADSC and ANA transplantation is a new therapeutic method for long distant peripheral nerve defects. Our data also provide evidence indicating the strong association of neurotrophic factor production to the regenerative potential of implanted ADSCs.