RESEARCH FOR BONE MARROW STROMAL CELLS (BMSC) TRANSPLANTATION THERAPY FOR INJURED CENTRAL NERVOUS SYSTEM USING BIOMATERIALS AND GENE ANALYSIS

使用生物材料和基因分析研究骨髓基质细胞 (BMSC) 移植治疗受伤的中枢神经系统

• 批准号: 15390426
• 负责人: IWASAKI Yoshinobu
• 金额: $ 8.06万
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390426/
• 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的培养体系，并将其移植到脑梗塞或脊髓损伤的动物体内。这些数据发表在《神经病理学》(2003)和《脑Res Protoc》(2004)上。我们从绿色荧光蛋白(GFP)转基因小鼠中分离出骨髓间充质干细胞，并将其移植到脑梗塞或脊髓损伤的小鼠体内。我们可以使用一种新的荧光成像技术，通过活体动物的头骨或硬脑膜显示移植的细胞。这些数据发表在《脑资源协议》(2004)和《神经创伤杂志》(2005)上。此外，通过放射自显影和荧光免疫染色证实，移植的BMSC可以改善脑梗塞和脊髓损伤周围的GABA受体功能。这些数据发表在《医学杂志》(2006)和《神经创伤杂志》(正在出版)上。我们还发现，当骨髓间充质干细胞移植到脑梗塞脑内时，可以积极地重复细胞的增殖，并将数据发表在Brain RES(2005)上。此外，我们评估了培养的骨髓间充质干细胞的基因表达谱，并阐明了骨髓间充质干细胞具有改变其基因表达谱以响应外界刺激的潜力。这些数据发表在《大脑资源》杂志(2006)上。我们利用器官型脊髓切片培养和一种新的“体外移植”模型，阐明了骨髓间充质干细胞具有降解脊髓中的细胞外基质并为神经元轴突延长产生化学吸引因子的潜力。这些数据已经提交给J神经外科公司。我们还发现，将纤维蛋白胶移植到大鼠脑冷损伤模型或脊髓半横断模型中，是一种适合作为BMSC支架的生物材料。这些数据已经准备好提交给神经外科和J神经外科学。

项目成果

In vivo fluorescence tracking of bone marrow stromal cells transplanted into rat spinal cord injury model.

骨髓基质细胞移植到大鼠脊髓损伤模型中的体内荧光追踪。

• 发表时间: 2005
• 期刊: J Neurotrauma 22
• 作者: Yano S;Kuroda S et al.;Yasuda H et al.;Yano S et al.;Yano S et al.;Yano S.Kuroda S et al.
• 通讯作者: Yano S.Kuroda S et al.

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

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

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

Kuroda S、Iwasaki Y 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。

Shichinohe H, Iwasaki Y, et al.: "FK506 reduces infarct volume due to permanent focal cerebral ischemia by maintaining BAD turnover and inhibiting cytochrome c release"Brain Res. 1001. 51-59 (2004)

Shichinohe H、Iwasaki Y 等人：“FK506 通过维持 BAD 更新和抑制细胞色素 c 释放来减少永久性局灶性脑缺血引起的梗塞体积”Brain Res。