BACKGROUND:We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice. OBJECTIVE:We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice. METHODS:Complete 5 mm defects were created in sciatic nerves and reconstructed using nerve conduits that were either uncoated or coated with mouse iPSC-derived neurospheres. The survival of the neurospheres on the nerve conduits was tracked using an in vivo imaging. The localization of the transplanted cells and regenerating axons was examined histologically. The gene expression levels in the nerve conduits were evaluated. RESULTS:The neurospheres survived for at least 14 days, peaking at 4–7 days after implantation. The grafted neurospheres remained as Schwann-like cells within the nerve conduits and migrated into the regenerated axons. The expression levels of ATF3, BDNF, and GDNF in the nerve conduit coated with neurospheres were upregulated. CONCLUSIONS:Mouse iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve defects in mice migrated into regenerating axons, survived as Schwann-like cells, and promoted axonal growth with an elevation in the expression of nerve regeneration-associated trophic factors.

中文翻译：

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移植神经导管的诱导多能干细胞衍生神经球促进小鼠周围神经再生的命运和贡献

背景：我们之前已经证明，涂有小鼠诱导多能干细胞 (iPSC) 衍生神经球的生物可吸收神经导管可加速小鼠周围神经的再生。目的：我们研究了移植有神经导管的 iPSC 衍生神经球治疗小鼠坐骨神经间隙的命运和效用。方法：在坐骨神经中产生完整的 5 mm 缺损，并使用未涂层或涂有小鼠 iPSC 衍生神经球的神经导管进行重建。使用体内成像跟踪神经导管上神经球的存活情况。组织学检查了移植细胞和再生轴突的定位。评估了神经导管中的基因表达水平。结果：神经球至少存活了 14 天，植入后4-7天达到高峰。移植的神经球在神经导管内保持为雪旺氏样细胞，并迁移到再生的轴突中。神经球包被的神经导管中ATF3、BDNF和GDNF的表达水平上调。结论：移植神经导管治疗小鼠坐骨神经缺损的小鼠 iPSC 衍生神经球迁移到再生轴突，作为雪旺氏细胞存活，并促进轴突生长，神经再生相关营养因子的表达升高。