Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Orthopaedic Surgery, Osaka General Hospital of West Japan Railway Company, Osaka, Japan.
Biomed Mater Eng. 2021;32(3):171-181. doi: 10.3233/BME-201182.
We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice.
We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice.
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.
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.
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.
我们之前的研究表明，包被有鼠诱导多能干细胞（iPSC）衍生神经球的可吸收神经导管加速了小鼠周围神经的再生。
我们研究了移植有 iPSC 衍生神经球的神经导管治疗小鼠坐骨神经间隙的命运和用途。
在坐骨神经上创建完整的 5mm 缺损，并使用未包被或包被有鼠 iPSC 衍生神经球的神经导管进行重建。使用体内成像技术追踪神经球在神经导管上的存活情况。通过组织学检查研究移植细胞和再生轴突的定位。评估神经导管中的基因表达水平。
神经球至少存活了 14 天，在植入后 4-7 天达到峰值。移植的神经球在神经导管内保持施万样细胞，并迁移到再生的轴突中。包被有神经球的神经导管中 ATF3、BDNF 和 GDNF 的表达水平上调。
移植有 iPSC 衍生神经球的神经导管治疗小鼠坐骨神经缺损后，神经球迁移到再生的轴突中，作为施万样细胞存活，并通过上调与神经再生相关的营养因子的表达促进轴突生长。
