Morita Eri, Watanabe Yasuhiro, Ishimoto Miho, Nakano Toshiya, Kitayama Michio, Yasui Kenichi, Fukada Yasuyo, Doi Koji, Karunaratne Asanka, Murrell Wayne G, Sutharsan Ratneswary, Mackay-Sim Alan, Hata Yoshio, Nakashima Kenji
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Exp Neurol. 2008 Oct;213(2):431-8. doi: 10.1016/j.expneurol.2008.07.011. Epub 2008 Jul 22.
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects motor neurons throughout the central nervous system. The extensive distribution of motor neurons is an obstacle to applying cell transplantation therapy for the treatment of ALS. To overcome this problem, we developed a cell transplantation method via the fourth cerebral ventricle in mice. We used mouse olfactory ensheathing cells (OECs) and rat mesenchymal stem cells (MSCs) as donor cells. OECs are reported to promote regeneration and remyelination in the spinal cord, while MSCs have a capability to differentiate into several types of specific cells including neural cells. Furthermore both types of cells can be relatively easily obtained by biopsy in human. Initially, we confirmed the safety of the operative procedure and broad distribution of grafted cells in the spinal cord using wild-type mice. After transplantation, OECs distributed widely and survived as long as 100 days after transplantation, with a time-dependent depletion of cell number. In ALS model mice, OEC transplantation revealed no adverse effects but no significant differences in clinical evaluation were found between OEC-treated and non-transplanted animals. After MSC transplantation into the ALS model mice, females, but not males, showed a statistically longer disease duration than the non-transplanted controls. We conclude that intrathecal transplantation could be a promising way to deliver donor cells to the central nervous system. Further experiments to elucidate relevant conditions for optimal outcomes are required.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，它选择性地影响整个中枢神经系统的运动神经元。运动神经元的广泛分布是应用细胞移植疗法治疗ALS的一个障碍。为了克服这个问题，我们开发了一种通过小鼠第四脑室进行细胞移植的方法。我们使用小鼠嗅鞘细胞（OECs）和大鼠间充质干细胞（MSCs）作为供体细胞。据报道，OECs可促进脊髓的再生和髓鞘再生，而MSCs有能力分化为包括神经细胞在内的几种特定类型的细胞。此外，这两种细胞在人体中都可以通过活检相对容易地获得。最初，我们使用野生型小鼠证实了手术操作的安全性以及移植细胞在脊髓中的广泛分布。移植后，OECs广泛分布并在移植后存活长达100天，细胞数量随时间逐渐减少。在ALS模型小鼠中，OEC移植未显示出不良反应，但在OEC治疗组和未移植组动物之间的临床评估中未发现显著差异。将MSCs移植到ALS模型小鼠后，雌性小鼠（而非雄性小鼠）的疾病持续时间在统计学上比未移植的对照组更长。我们得出结论，鞘内移植可能是将供体细胞输送到中枢神经系统的一种有前景的方法。需要进一步的实验来阐明实现最佳结果的相关条件。
