The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries
The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries
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DOI：
10.3171/2012.7.jns111503
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发表时间：
2012-10-01
影响因子：
4.1
通讯作者：
Ochi, Mitsuo
中科院分区：
文献类型：
--
作者：
Ohtsubo, Shin;Ishikawa, Masakazu;Ochi, Mitsuo
对象。CD133（+）细胞有可能促进周围神经损伤后的组织学和功能恢复。然而，从人外周血中安全获得的CD133（+）细胞数量非常有限。为了解决这一问题，作者使用无血清扩增培养方法扩增人外周血中的CD133（+）细胞，并将这些体外扩增细胞移植到大鼠坐骨神经缺损模型中。本研究的目的是确定体外扩增的CD133（+）细胞诱导或增强损伤周围神经修复的潜力。磷酸盐缓冲盐水（PBS组[第1组]）。将10(5)个新鲜CD133（+）细胞（新鲜组[2组]）、10(5)个体外扩增CD133（+）细胞（扩增组[3组]）或10(4)个新鲜CD133（+）细胞（低剂量组[4组]）包埋在离体胶原凝胶中，移植到硅胶管中，然后用于胸大鼠坐骨神经15 mm缺损的桥接（每组10只）。术后8周，对再生组织进行组织学和功能评价。培养1周后，细胞数量增加9.6 +/- 3.3倍。通过荧光活化细胞分选分析，证实了初始新分离的CD133（+）细胞群含有93.22% +/- 0.30%的CD133（+）细胞，进一步证实扩增后的细胞纯度为59.02% +/- 1.58%的CD133（+）细胞。然而，在组织学和功能上，2组和3组的所有大鼠和4组的10只大鼠中有6只发现了桥接缺损的再生神经。在第一组中，没有任何大鼠的神经再生来桥接缺损。作者的研究结果表明，来源于人外周血的体外扩增CD133（+）细胞具有与新鲜CD133（+）细胞相似的治疗周围神经损伤的潜力。体外扩增CD133（+）细胞而不降低其功能的方法代表了一种在临床环境中开发神经缺陷细胞治疗的新方法。(http://thejns.org/doi/abs/10.3171/2012.7.JNS111503)
Object. CD133(+) cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133(+) cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133(+) cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133(+) cells to induce or enhance the repair of injured peripheral nerves.Methods. Phosphate-buffered saline (PBS group [Group 1]). 10(5) fresh CD133(+) cells (fresh group [Group 2]), 10(5) ex vivo expanded CD133(+) cells (expansion group [Group 3]), or 10(4) fresh CD133(+) cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed.Results. After 1 week of expansion culture, the number of cells increased 9.6 +/- 3.3 fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133(+) cell population contained 93.22% +/- 0.30% CD133(+) cells and further confirmed that the expanded cells had a purity of 59.02% +/- 1.58% CD133(+) cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1.Conclusions. The authors' results show that ex vivo expanded CD133(+) cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133(+) cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133(+) cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting. (http://thejns.org/doi/abs/10.3171/2012.7.JNS111503)