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人外周血来源的CD133+细胞移植后周围神经的再生

Regeneration of peripheral nerve after transplantation of CD133+ cells derived from human peripheral blood.

作者信息

Kijima Yasumu, Ishikawa Masakazu, Sunagawa Toru, Nakanishi Kazuyoshi, Kamei Naosuke, Yamada Kiyotaka, Tanaka Nobuhiro, Kawamata Seiichi, Asahara Takayuki, Ochi Mitsuo

机构信息

Department of Orthopedic Surgery, Graduate School of Biomedical Sciences, Japan.

出版信息

J Neurosurg. 2009 Apr;110(4):758-67. doi: 10.3171/2008.3.17571.

DOI:10.3171/2008.3.17571
PMID:19012485
Abstract

OBJECT

Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult to achieve full functional recovery in humans following extended peripheral nerve lesions. In this study, the authors examined the use of blood-derived CD133(+) cells in promoting the repair of peripheral nerve defects.

METHODS

The authors transplanted phosphate-buffered saline (control), mononuclear cells, or CD133(+) cells embedded in atelocollagen gel into a silicone tube that was used to bridge a 15-mm defect in the sciatic nerve of athymic rats (12 animals in each group). At 8 weeks postsurgery, molecular, histological, and functional evaluations were performed in regenerated tissues.

RESULTS

The authors found that sciatic nerves in which a defect had been made were structurally and functionally regenerated within 8 weeks after CD133(+) cell transplantation. From macroscopic evaluation, massive nervelike tissues were confirmed only in rats with CD133(+) cell transplantation compared with the other groups. Morphological regeneration in the samples after CD133(+) cell transplantation, as assessed using toluidine blue staining, was enhanced significantly in terms of the number of myelinated fibers, axon diameter, myelin thickness, and percentage of neural tissue. Compound muscle action potentials were observed only in CD133(+) cell-treated rats. Furthermore, it was demonstrated that the transplanted CD133(+) cells differentiated into Schwann cells by 8 weeks after transplantation.

CONCLUSIONS

The results show that CD133(+) cells have potential for enhancement of histological and functional recovery from peripheral nerve injury. This attractive cell source could be purified easily from peripheral blood and could be a feasible autologous candidate for peripheral nerve injuries in the clinical setting.

摘要

目的

尽管在外周神经损伤与再生领域已付出巨大努力,但人类外周神经发生广泛性损伤后,仍难以实现完全功能恢复。在本研究中,作者探讨了利用血液来源的CD133(+)细胞促进外周神经缺损修复的作用。

方法

作者将磷酸盐缓冲盐水(对照组)、单核细胞或包埋于脱细胞胶原凝胶中的CD133(+)细胞移植到硅胶管中,该硅胶管用于桥接无胸腺大鼠坐骨神经15毫米的缺损(每组12只动物)。术后8周,对再生组织进行分子、组织学和功能评估。

结果

作者发现,CD133(+)细胞移植后8周内,有缺损的坐骨神经在结构和功能上均实现再生。从宏观评估来看,与其他组相比,仅在接受CD133(+)细胞移植的大鼠中确认有大量神经样组织。使用甲苯胺蓝染色评估,CD133(+)细胞移植后样本中的形态学再生在有髓纤维数量、轴突直径、髓鞘厚度和神经组织百分比方面均显著增强。仅在接受CD133(+)细胞治疗的大鼠中观察到复合肌肉动作电位。此外,已证明移植的CD133(+)细胞在移植后8周内分化为雪旺细胞。

结论

结果表明,CD133(+)细胞具有促进外周神经损伤组织学和功能恢复的潜力。这种有吸引力的细胞来源可轻松从外周血中纯化,可能是临床环境中外周神经损伤可行的自体细胞候选物。

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