Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Biochem Biophys Res Commun. 2012 Mar 2;419(1):130-5. doi: 10.1016/j.bbrc.2012.01.154. Epub 2012 Feb 7.
In spite of the extensive research using induced pluripotent stem (iPS) cells, the therapeutic potential of iPS cells in the treatment of peripheral nerve injury is largely unknown. In this study, we repaired peripheral nerve gaps in mice using tissue-engineered bioabsorbable nerve conduits coated with iPS cell-derived neurospheres. The secondary neurospheres derived from mouse iPS cells were suspended in each conduit (4000,000 cells per conduit) and cultured in the conduit in three-dimensional (3D) culture for 14 days. We then implanted them in the mouse sciatic nerve gaps (5 mm) (iPS group; n=10). The nerve conduit alone was implanted in the control group (n=10). After 4, 8 and 12 weeks, motor and sensory functional recovery in mice were significantly better in the iPS group. At 12 weeks, all the nerve conduits remained structurally stable without any collapse and histological analysis indicated axonal regeneration in the nerve conduits of both groups. However, the iPS group showed significantly more vigorous axonal regeneration. The bioabsorbable nerve conduits created by 3D-culture of iPS cell-derived neurospheres promoted regeneration of peripheral nerves and functional recovery in vivo. The combination of iPS cell technology and bioabsorbable nerve conduits shows potential as a future tool for the treatment of peripheral nerve defects.
尽管使用诱导多能干细胞（iPS 细胞）进行了广泛的研究，但 iPS 细胞在治疗周围神经损伤方面的治疗潜力在很大程度上仍是未知的。在这项研究中，我们使用涂覆有 iPS 细胞衍生的神经球的组织工程生物可吸收神经导管修复了小鼠的周围神经间隙。从小鼠 iPS 细胞中衍生的次级神经球悬浮在每个导管中（每个导管 400 万个细胞），并在三维（3D）培养中在导管中培养 14 天。然后，我们将它们植入小鼠坐骨神经间隙（5 毫米）（iPS 组；n=10）。单独将神经导管植入对照组（n=10）。4、8 和 12 周后，iPS 组中小鼠的运动和感觉功能恢复明显更好。在 12 周时，所有神经导管均保持结构稳定，没有任何塌陷，组织学分析表明两组神经导管中均有轴突再生。然而，iPS 组显示出更活跃的轴突再生。由 iPS 细胞衍生的神经球的 3D 培养创建的生物可吸收神经导管促进了周围神经的再生和体内功能的恢复。iPS 细胞技术和生物可吸收神经导管的结合显示出作为治疗周围神经缺损的未来工具的潜力。
