A novel cell transplantation protocol and its application to an ALS mouse model
A novel cell transplantation protocol and its application to an ALS mouse model
复制标题
DOI：
10.1016/j.expneurol.2008.07.011
复制
发表时间：
2008-10
影响因子：
5.3
通讯作者：
Eri Morita;Yasuhiro Watanabe;M. Ishimoto;Toshiya Nakano;M. Kitayama;K. Yasui;Yasuyo Fukada;K. Doi;Asanka Karunaratne;W. Murrell;R. Sutharsan;A. Mackay-Sim;Y. Hata;K. Nakashima
中科院分区：
文献类型：
--
作者：
Eri Morita;Yasuhiro Watanabe;M. Ishimoto;Toshiya Nakano;M. Kitayama;K. Yasui;Yasuyo Fukada;K. Doi;Asanka Karunaratne;W. Murrell;R. Sutharsan;A. Mackay-Sim;Y. Hata;K. Nakashima
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（OEC）和大鼠间充质干细胞（MSC）作为供体细胞。据报道，OEC 可以促进脊髓的再生和髓鞘再生，而 MSC 则能够分化成多种类型的特定细胞，包括神经细胞。此外，这两种类型的细胞都可以通过人体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过程的安全性和移植细胞在脊髓中的广泛分布。移植后，OEC 分布广泛，存活时间长达 100 天，细胞数量呈时间依赖性减少。在 ALS 模型小鼠中，OEC 移植没有显示任何副作用，但 OEC 治疗和未移植的动物之间的临床评估没有显着差异。将间充质干细胞移植到 ALS 模型小鼠中后，雌性小鼠（而非雄性小鼠）的疾病持续时间在统计上比未移植的对照组更长。我们的结论是，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途的方法。需要进一步的实验来阐明最佳结果的相关条件。
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.