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

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。我们利用一种新颖的荧光成像技术，可以在活体动物移植后4周内通过硬脑膜观察移植细胞。这些数据发表在J神经创伤杂志（2005）上。此外，我们通过放射自显影和荧光免疫染色证实移植的BMSC可以改善脑梗死和脊髓损伤周围的GABA受体功能。这些数据发表在《核医学杂志》（2006）和《神经创伤杂志》（2007）上。我们还发现，当移植到梗死脑中时，BMSC积极重复细胞增殖，并将数据发表在brain Res（2005）上。我们评估了培养的骨髓间充质干细胞的基因表达谱，并澄清了骨髓间充质干细胞在响应外部刺激时具有改变其基因表达谱的潜力。这些数据发表在Brain Res（2006）上。我们已经通过一种新的“体外移植”模型阐明了BMSC具有降解脊髓细胞外基质的潜力，并产生神经元轴突伸长的化学引诱因子。该数据已提交给神经康复和神经修复。我们还利用敲除CXCR4的小鼠阐明了CXCR4/SDF-1系统在移植BMSC的增殖和迁移中是必不可少的。这些数据已提交给Brain Res.使用共培养模式，我们还澄清了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，在大鼠脑冷损伤模型或脊髓半断模型中，纤维蛋白胶是一种适合作为BMSC支架的生物材料。这些数据已准备好提交给神经外科和神经创伤杂志。

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.