Injured nerves cannot regenerate on their own, and a lack of engraftable human nerves has been a major obstacle in cell-based therapies for regenerating damaged nerves. A monolayer culture approach to obtain adherent neural stem cells from human embryonic stem cells (hESC-NSCs) was established, and the greatest number of stemness characteristics were achieved by the eighth generation of hESC-NSCs (P8 hESC-NSCs). To overcome deficits in cell therapy, we used microvesicles secreted from P8 hESC-NSCs (hESC-NSC-MVs) instead of entire hESC-NSCs. To investigate the therapeutic efficacy of hESC-NSC-MVs in vitro, hESC-NSC-MVs were cocultured with dorsal root ganglia to determine the length of axons. In vivo, we transected the sciatic nerve in SD rats and created a 5-mm gap. A sciatic nerve defect was bridged using a silicone tube filled with hESC-NSC-MVs (45 μg) in the MVs group, P8 hESC-NSCs (1 × 10⁶ single cells) in the cell group and PBS in the control group. The hESC-NSC-MVs group showed better morphological recovery and a significantly greater number of regenerated axons than the hESC-NSCs group 12 weeks after nerve injury. These results indicated that the hESC-NSC-MVs group had the greatest ability to repair and reconstruct nerve structure and function. As a result, hESC-NSC-MVs may have potential for applications in the field of nerve regenerative repair.

中文翻译：

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通过移植源自胚胎干细胞的人神经干细胞的微泡来再生坐骨神经。

受损的神经无法自行再生，而缺乏可移植的人类神经一直是基于细胞的受损神经再生疗法的主要障碍。建立了从人胚胎干细胞（hESC-NSC）中获得贴壁神经干细胞的单层培养方法，并且第八代hESC-NSC（P8 hESC-NSC）实现了最大数量的干性特征。为了克服细胞疗法的缺陷，我们使用 P8 hESC-NSC (hESC-NSC-MV) 分泌的微泡而不是整个 hESC-NSC。为了研究 hESC-NSC-MV 的体外治疗效果，将 hESC-NSC-MV 与背根神经节共培养以确定轴突的长度。在体内，我们横断了 SD 大鼠的坐骨神经并创建了 5 毫米的间隙。MV组使用填充hESC-NSC-MV（45 μg）的硅胶管桥接坐骨神经缺损，细胞组使用填充P8 hESC-NSC（1 × 10 6 个单细胞），对照组使用^PBS。神经损伤后12周，hESC-NSC-MVs组比hESC-NSCs组表现出更好的形态恢复和明显更多的再生轴突数量。这些结果表明hESC-NSC-MVs组具有最大的修复和重建神经结构和功能的能力。因此，hESC-NSC-MVs可能在神经再生修复领域具有应用潜力。