Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell-derived astrocytes in a rat spinal cord injury model
Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell-derived astrocytes in a rat spinal cord injury model
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DOI：
10.3171/2011.7.spine10775
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发表时间：
2011-12-01
影响因子：
2.8
通讯作者：
Yamazaki, Masashi
中科院分区：
文献类型：
--
作者：
Hayashi, Koichi;Hashimoto, Masayuki;Yamazaki, Masashi
Object.自体诱导多能干细胞（iPSC）的临床应用可以避免与胚胎干细胞相关的免疫排斥和生物伦理问题。脊髓损伤（SCI）是一种具有长期残疾的毁灭性创伤，目前的治疗方法并不令人满意。在本研究中，作者使用神经干球（NSS）方法将iPSCs分化为星形胶质细胞，并在其移植到损伤的大鼠脊髓后进行评估。使用NSS方法分化诱导的多能干细胞衍生的星形胶质细胞，并在基于SCI的脊髓挫伤后3天和7天注射。以相同的方式向对照大鼠注射DMEM。运动恢复进行了评估，为8周，并在8周的感觉和运动测试进行了评价。然后评估免疫组织学参数。移植受体存活8周，无肿瘤形成。移植细胞的突起沿着纵轴伸展，但它们不与宿主GFAP阳性星形胶质细胞的突起融合。以3种方式评估运动，但与8周后的DMEM处理对照大鼠相比，没有一种测试检测到统计学显著的改善。相反，iPSC移植导致对机械刺激的敏感性甚至比DMEM处理更高。星形胶质细胞可以通过血清处理衍生自iPSC的NSS产生的细胞来产生。然而，移植此类细胞不太适合修复SCI。(DOI：10.3171/2011.7.SPINEI 0775）
Object. Clinical use of autologous induced pluripotent stem cells (iPSCs) could circumvent immune rejection and bioethical issues associated with embryonic stem cells. Spinal cord injury (SCI) is a devastating trauma with long-lasting disability, and current therapeutic approaches are not satisfactory. In the present study, the authors used the neural stem sphere (NSS) method to differentiate iPSCs into astrocytes, which were evaluated after their transplantation into injured rat spinal cords.Methods. Induced pluripotent stein cell derived astrocytes were differentiated using the NSS method and injected 3 and 7 days after spinal contusion based SCI. Control rats were injected with DMEM in the same manner. Locomotor recovery was assessed for 8 weeks, and sensory and locomotion tests were evaluated at 8 weeks. Immunohistological parameters were then assessed.Results. Transplant recipients lived for 8 weeks without tumor formation. Transplanted cells stretched their processes along the longitudinal axis, but they did not merge with the processes of host GFAP-positive astrocytes. Locomotion was assessed in 3 ways, but none of the tests detected statistically significant improvements compared with DMEM-treated control rats after 8 weeks. Rather, iPSC transplantation caused even greater sensitivity to mechanical stimulus than DMEM treatment.Conclusions. Astrocytes can be generated by serum treatment of NSS-generated cells derived from iPSCs. However, transplantation of such cells is poorly suited for repairing SCI. (DOI: 10.3171/2011.7.SPINEI0775)