Yamaguchi Satoshi, Kuroda Satoshi, Kobayashi Hiroyuki, Shichinohe Hideo, Yano Shunsuke, Hida Kazutoshi, Shinpo Kazuyoshi, Kikuchi Seiji, Iwasaki Yoshinobu
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Sapporo 060-8638, Japan.
Brain Res. 2006 May 4;1087(1):15-27. doi: 10.1016/j.brainres.2006.02.127. Epub 2006 Apr 13.
Bone marrow stromal cells (BMSC) have been anticipated as a donor for cell type for transplantation therapy in various neurological disorders. However, their neurogenic capacity still remains undetermined. In this study, we aimed to clarify whether in vitro chemical treatment promotes their neuronal differentiation on the level of gene expression. Mice BMSC were cultured with medium supplemented with DMSO, retinoic acid, and basic fibroblast growth factor, and their morphology and expression of neuronal markers were evaluated. Subsequently, using microarray and RT-PCR techniques, the treatment-induced changes in the gene expression profile were analyzed. After exposure to the medium, the BMSC simulated a neuron-like appearance and increased their immunoreactivity for nestin and Tuj-1. Microarray analysis revealed that the BMSC per se express the multilineage cellular genes, including those associated with the neuron. Chemical treatment significantly decreased the expression of genes related to mesenchymal cells and increased the expression of 5 neuron-associated genes. Microarray and RT-PCR analyses also demonstrated that the BMSC express the genes for several growth factors including NGF-beta and BDNF, indicating their therapeutic role in protecting the injured central nervous system. The present results suggest that at least a certain subpopulation of the BMSC have the potential to alter their gene expression profile in response to the surrounding environment and may possibly protect the host tissue by secreting neuroprotective factors.
骨髓基质细胞（BMSC）已被视为用于各种神经系统疾病移植治疗的细胞类型供体。然而，它们的神经发生能力仍未确定。在本研究中，我们旨在阐明体外化学处理是否能在基因表达水平上促进其神经元分化。将小鼠BMSC培养于添加有二甲基亚砜、视黄酸和碱性成纤维细胞生长因子的培养基中，并评估其形态和神经元标志物的表达。随后，使用微阵列和逆转录-聚合酶链反应（RT-PCR）技术分析处理诱导的基因表达谱变化。暴露于该培养基后，BMSC呈现出神经元样外观，并增加了其对巢蛋白和Tuj-1的免疫反应性。微阵列分析显示，BMSC本身表达多谱系细胞基因，包括那些与神经元相关的基因。化学处理显著降低了与间充质细胞相关基因的表达，并增加了5个与神经元相关基因的表达。微阵列和RT-PCR分析还表明，BMSC表达包括神经生长因子-β（NGF-β）和脑源性神经营养因子（BDNF）在内的几种生长因子的基因，表明它们在保护受损中枢神经系统中的治疗作用。目前的结果表明，至少BMSC的某些亚群有潜力根据周围环境改变其基因表达谱，并可能通过分泌神经保护因子来保护宿主组织。
