RESEARCH FOR CELL TRANSPLANTATION THERAPY FOR CEREBRAL INFARCTION AND SPINAL CORD INJURY USING BONE MARROW STROMAL CELLS (BMSC)

使用骨髓基质细胞 (BMSC) 进行脑梗塞和脊髓损伤的细胞移植治疗研究

• 批准号: 14370424
• 负责人: KURODA Satoshi
• 金额: $ 7.68万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370424/
• 关键词: Cerebral infarction; Spinal cord injury; Bone marrow stromal cells; Transplantation; Differentiation; Migration; Biomaterial; Neuroprotection; Regeneration; bone marrow; stromal cell; central nervous system; cerebral infarct; spinal cord inju

We have established the culture system of the bone marrow stromal cells (BMSC) obtained from the rats and mice, and transplanted them into the animals subjected to cerebral infarction or spinal cord injury. These data were published in Neuropathology (2003) and Brain Res Protoc (2004). We isolated the BMSC from the green fluorescence protein (GFP)-transgenic mice and transplanted them into the mice subjected to cerebral infarction or spinal cord injury. We could visualize the transplanted cells through the skull or the dura mater in the living animals, using a novel fluorescence imaging technique. These data were published in Brain Res Protoc (2004) and 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 (in press). We also found that the BMSC actively repeat cell proliferation when transplanted into infarct brain, and published the data in Brain Res (2005). In addition, 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 organotypic spinal cord slice culture and a novel "in vitro transplantation" model. The data have been submitted to J Neurosurg. 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.

我们建立了大鼠和小鼠骨髓基质细胞（BMSC）的培养体系，并将其移植到脑梗死或脊髓损伤的动物体内。这些数据发表在Neuropathology（2003）和Brain Res Protoc（2004）上。我们从绿色荧光蛋白（GFP）转基因小鼠中分离出BMSC，并将其移植到脑梗死或脊髓损伤的小鼠体内。利用一种新的荧光成像技术，我们可以通过活体动物的头骨或硬脑膜观察移植的细胞。这些数据发表在Brain Res Protoc（2004）和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（出版中）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。此外，我们评估了培养的BMSC中的基因表达谱，并阐明了BMSC具有改变其基因表达谱以响应外部刺激的潜力。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，使用器官型脊髓切片培养和一种新的“体外移植”模型。数据已提交给J Neurosurg。我们还发现，纤维蛋白胶是一种合适的生物材料，可以作为BMSC移植到大鼠脑冷损伤模型或脊髓半切模型中的支架材料。这些数据已准备提交给Neurosurgery和J Neurotrauma。

项目成果

Lee J B, Kuroda S et al.: "Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice"Neuropathology. 23. 167-178 (2003)

Lee J B，Kuroda S等：“移植到小鼠脑梗塞和脊髓损伤后核荧光标记的骨髓基质细胞的迁移和分化”神经病理学。

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

Kuroda S et al.: "Reduced blood flow and preserved vasoreactivity characterize oxygen hypometabolism due to incomplete infarction in occlusive carotid artery diseases"J Nucl Med. (in press).

Kuroda S 等人：“闭塞性颈动脉疾病中不完全梗塞导致血流量减少和血管反应性保留是氧代谢低下的特征”J Nucl Med。

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

• 发表时间: 2006-03
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: H. Shichinohe;S. Kuroda;S. Yano;T. Ohnishi;H. Tamagami;K. Hida;Y. Iwasaki

A pre-clinical assessment model of rat autogeneic bone marrow stromal cell transplantation into the central nervous system

• DOI: 10.1016/j.brainresprot.2004.09.004
• 发表时间: 2004-11-01
• 期刊: BRAIN RESEARCH PROTOCOLS
• 作者: Lee, JB;Kuroda, S;Iwasaki, Y
• 通讯作者: Iwasaki, Y