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

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BMSC，并将其移植到脑梗死或脊髓损伤的小鼠中。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。

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.