Uemura Takuya, Takamatsu Kiyohito, Ikeda Mikinori, Okada Mitsuhiro, Kazuki Kenichi, Ikada Yoshito, Nakamura Hiroaki
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Japan.
Biomed Mater Eng. 2011;21(5-6):333-9. doi: 10.3233/BME-2012-0680.
We previously reported a bioabsorbable nerve conduit coated with Schwann cells for the treatment of peripheral nerve defects. Since there have been dramatic developments in induced pluripotent stem (iPS) cells in recent years, the purpose of the present study was to create a tissue-engineered nerve conduit coated with iPS cell-derived neurospheres. Such a conduit was constructed by three-dimensional (3D)-culture of these cells using a bioabsorbable polymer conduit as a scaffold. The nerve conduit was composed of a mesh of poly L-lactide, and a porous sponge of 50% poly L-lactide and 50% poly ε-caprolactone. The primary and secondary neurospheres (PNS and SNS, respectively) induced from iPS cells were suspended in individual conduits. The conduits were incubated for 7 or 14 days in vitro and then evaluated using immunohistochemistry. All of the 7- and 14-day differentiated PNS and SNS were observed to have adhered to the inner surface of the conduits and to have migrated into the inner porous sponge. The engrafted cells were positive for anti-Tuj1, -S-100 and -GFAP antibodies, indicating that their pluripotent ability to form neural or glial cells was maintained. These findings indicate the feasibility of creating nerve conduits coated with a 3D-culture of iPS cell-derived neurospheres for the treatment of peripheral nerve defects.
我们之前报道过一种涂有雪旺细胞的生物可吸收神经导管用于治疗周围神经缺损。近年来诱导多能干细胞（iPS细胞）有了显著发展，本研究的目的是创建一种涂有iPS细胞来源神经球的组织工程神经导管。这种导管是通过以生物可吸收聚合物导管为支架对这些细胞进行三维（3D）培养构建而成。神经导管由聚L-丙交酯网和50%聚L-丙交酯与50%聚ε-己内酯的多孔海绵组成。将从iPS细胞诱导产生的初级和次级神经球（分别为PNS和SNS）悬浮于各个导管中。导管在体外培养7天或14天，然后使用免疫组织化学进行评估。观察到所有7天和14天分化的PNS和SNS均附着于导管内表面并迁移至内部多孔海绵中。植入的细胞对抗Tuj1、-S-100和-GFAP抗体呈阳性，表明它们形成神经或神经胶质细胞的多能能力得以维持。这些发现表明创建涂有iPS细胞来源神经球3D培养物的神经导管用于治疗周围神经缺损具有可行性。
