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使用神经导管结合诱导多能干细胞技术和碱性成纤维细胞生长因子药物递送系统加速周围神经再生

Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system.

作者信息

Ikeda Mikinori, Uemura Takuya, Takamatsu Kiyohito, Okada Mitsuhiro, Kazuki Kenichi, Tabata Yasuhiko, Ikada Yoshito, Nakamura Hiroaki

机构信息

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

J Biomed Mater Res A. 2014 May;102(5):1370-8. doi: 10.1002/jbm.a.34816. Epub 2013 Jun 11.

Abstract

Various modifications including addition of Schwann cells or incorporation of growth factors with bioabsorbable nerve conduits have been explored as options for peripheral nerve repair. However, no reports of nerve conduits containing both supportive cells and growth factors have been published as a regenerative therapy for peripheral nerves. In the present study, sciatic nerve gaps in mice were reconstructed in the following groups: nerve conduit alone (control group), nerve conduit coated with induced pluripotent stem cell (iPSc)-derived neurospheres (iPSc group), nerve conduit coated with iPSc-derived neurospheres and basic fibroblast growth factor (bFGF)-incorporated gelatin microspheres (iPSc + bFGF group), and autograft. The fastest functional recovery and the greatest axon regeneration occurred in the autograft group, followed in order by the iPSc + bFGF group, iPSc group, and control group until 12 weeks after reconstruction. Thus, peripheral nerve regeneration using nerve conduits and functional recovery in mice was accelerated by a combination of iPSc-derived neurospheres and a bFGF drug delivery system. The combination of all three fundamental methodologies, iPSc technology for supportive cells, bioabsorbable nerve conduits for scaffolds, and a bFGF drug delivery system for growth factors, was essential for peripheral nerve regenerative therapy.

摘要

人们已经探索了各种改良方法,包括添加施万细胞或将生长因子与可生物吸收的神经导管相结合,作为周围神经修复的选择。然而,尚未有关于含有支持细胞和生长因子的神经导管作为周围神经再生疗法的报道。在本研究中,对小鼠的坐骨神经缺损进行了如下分组重建:单纯神经导管(对照组)、涂有诱导多能干细胞(iPSc)来源的神经球的神经导管(iPSc组)、涂有iPSc来源的神经球和掺入碱性成纤维细胞生长因子(bFGF)的明胶微球的神经导管(iPSc + bFGF组),以及自体移植。自体移植组功能恢复最快,轴突再生最多,其次依次是iPSc + bFGF组、iPSc组和对照组,直至重建后12周。因此,iPSc来源的神经球和bFGF药物递送系统的组合加速了小鼠使用神经导管的周围神经再生和功能恢复。支持细胞的iPSc技术、支架的可生物吸收神经导管和生长因子的bFGF药物递送系统这三种基本方法的组合,对于周围神经再生治疗至关重要。

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