RESEARCH FOR BONE MARROW STROMAL CELLS (BMSC) TRANSPLANTATION THERAPY FOR INJURED CENTRAL NERVOUS SYSTEM FOCUSED ON AXON EXTENSION FROM THE HOST NEURONS

针对受损中枢神经系统的骨髓基质细胞 (BMSC) 移植治疗研究重点关注宿主神经元的轴突延伸

• 批准号: 17591496
• 负责人: KOBAYASHI H.
• 金额: $ 2.18万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591496/
• 关键词: Cerebral infarction; Spinal cord injury; Bone marrow stromal cells; Transplantation; Differentiation; Migration; Bone carrow stromal cell; Diffuse brain injury; Cognitive function; Regererative medicine; DNA microarray; Cerebral stroke; Biomat

We isolated the BMSC from the green fluorescence protein (GFP)-transgenic mice and transplanted them into the mice subjected to spinal cord injury. We could visualize the transplanted cells through the dura mater in the living animals for 4 weeks after transplantation, using a novel fluorescence imaging technique. These data were published in J Neurotrauma (2005). Furthermore, we have confirmed that the transplanted BMSC could improve the GABA receptor function around cerebral infarction and spinal cord injury, using autoradiography and fluorescence immunostaining. These data were published in J Nucl Med (2006) and J Neurotrauma (2007). We also found that the BMSC actively repeat cell proliferation when transplanted into infarct brain, and published the data in Brain Res (2005). We assessed gene expression profile in the cultured BMSC and clarified that the BMSC have the potential to alter their gene expression profile in response to external stimuli. The data were published in Brain Res (2006). We have clarified that the BMSC have the potential to degrade the extracellular matrix in the spinal cord and produce the chemo-attractant factor for axon elongation of the neurons, using a novel "in vitro transplantation" model. The data have been submitted to Neurorehab and Neural Repair. We have also clarified that CXCR4/SDF-1 system is essential in the proliferation and migration of the transplanted BMSC, using the CXCR4-knock out mice. The data have been submitted to Brain Res. Using co-culture paradigm, we have also clarified that the BMSC have the potential to differentiate into the neural cells and protect the neurons exposed to glutamate. The data have been submitted to J Neurosci Res. We have also found that fibrin glue is a suitable biomaterial as a scaffold for the BMSC when transplanted into brain cold injury model or spinal cord hemi-section model of the rats. These data has been prepared for submission to Neurosurgery and J Neurotrauma.

我们从绿色荧光蛋白（GFP）转基因小鼠中分离BMSC，并将其移植到脊髓损伤小鼠体内。移植后4周，我们可以通过活体动物的硬脑膜观察移植的细胞，使用一种新的荧光成像技术。这些数据发表在J Neurotrauma（2005）上。此外，我们还通过放射自显影和荧光免疫染色证实了移植的BMSC可以改善脑梗死和脊髓损伤周围的GABA受体功能。这些数据发表在J Nucl Med（2006）和J Neurotrauma（2007）上。我们还发现，当移植到梗死脑中时，BMSC积极地重复细胞增殖，并将数据发表在Brain Res（2005）中。我们评估了培养的BMSC的基因表达谱，并阐明了BMSC有可能改变其基因表达谱，以响应外部刺激。这些数据发表在Brain Res（2006）上。我们已经阐明，骨髓间充质干细胞有潜力降解脊髓细胞外基质，并产生化学吸引因子的轴突伸长的神经元，使用一种新的“体外移植”模型。这些数据已提交给神经康复和神经修复。我们还阐明了CXCR 4/SDF-1系统在移植的BMSC的增殖和迁移中是必不可少的，使用CXCR 4敲除小鼠。这些数据已经提交给Brain Res.使用共培养模式，我们还阐明了BMSC具有分化为神经细胞和保护暴露于谷氨酸的神经元的潜力。我们还发现，纤维蛋白胶是一种合适的生物材料作为支架的BMSC移植到脑冷损伤模型或脊髓半切模型的大鼠。这些数据已准备提交给Neurosurgery和J Neurotrauma。

项目成果

The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)—a preliminary study using microarray analysis

• DOI: 10.1016/j.brainres.2006.02.127
• 发表时间: 2006-05
• 期刊: Brain Research
• 影响因子: 2.9
• 作者: S. Yamaguchi;S. Kuroda;Hiroyuki Kobayashi;H. Shichinohe;S. Yano;K. Hida;K. Shinpo;S. Kikuchi;Y. Iwasaki

The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)

神经元诱导对骨髓基质细胞（BMSC）基因表达谱的影响

• 发表时间: 2006
• 期刊: Brain Res 1087
• 作者: Yamaguchi S;Kuroda S;et al.
• 通讯作者: et al.

Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation

脑微血管内皮细胞对晚期糖基化终产物诱导的组织因子上调的敏感性

• 发表时间: 2006
• 期刊: Brain Res 1108
• 作者: Niiya Y;Kuroda S;et al.
• 通讯作者: et al.

Bone marrow stromal cell transplantation preserves gamma- aminobutyric acid (GABA) receptor function in injured spinal cord.

骨髓基质细胞移植可保留受损脊髓中的γ-氨基丁酸（GABA）受体功能。

• 发表时间: 2006
• 期刊: J Neurotrauma 23(11)
• 作者: Yano S;Kuroda S et al.
• 通讯作者: Kuroda S et al.

Cerebral oxygen metabolism and neuronal integrity in patients with impaired vasoreactivity due to occlusive carotid artery diseases

颈动脉闭塞性疾病导致血管反应性受损患者的脑氧代谢和神经元完整性

• 发表时间: 2006
• 期刊: Stroke 37
• 作者: Kuroda;et al.
• 通讯作者: et al.