Angiogenesis with bone marrow cells and gene therapy

为了开发闭塞性脑血管病的新治疗模式，我们尝试将骨髓细胞治疗与病毒载体基因治疗相结合。我们执行了接下来的3个项目。1)用表达fgf -2的腺病毒载体直接基因治疗MCA闭塞大鼠侧脑室。2)单纯疱疹病毒（HSV）表达FGF-2、VEGF和HGF的新载体的研制。利用这种新的载体将上述基因转移到骨髓细胞中也是一种新的尝试。3)利用间充质间质细胞（MSC）和新研制的HSV载体进行治疗实验。结果：1)直接基因传递FGF-2可减小脑梗死面积，改善MCA闭塞后神经系统症状。2)新构建的HSV在间充质间质细胞中表现出明显的基因转导效果，在间充质间质间质细胞中表现出稳定而强的基因表达。MSC中未发现病毒复制。3)瘤内移植MSC能改善MCA闭塞大鼠的神经系统症状，而HSV载体转染HGF基因的MSC对模型大鼠的神经系统症状改善更明显。

To develop the new therapeutic modality for occlusive cerebrovascular disease, we try to combine the cell therapy using bone marrow cells and gene therapy using viral vectors. We performed next 3 projects.1)Direct gene therapy using FGF-2-expressing adenoviral vectors into lateral ventricle in MCA occlusiojn rat.2)Development of new, replication incompetent herpes simplex virus (HSV) vector expressing FGF-2, VEGF and HGF. Also new attempt to transfer the above gene into bone marrow cells using this new vectors.3)Therapeutic experiment using mesenchymal stromal cells (MSC) and this new developed HSV vectors.Results :1)Direct gene delivery of FGF-2 decreased the infarction size and improved the neurological symptom after MCA occlusion.2)Newly constructed HSV showed marked gene transduction efficacy into mesenchymal stromal cells and exhibited stable and strong gene expression in the MSC. No viral replication in MSC was recognized.3)Intralesional transplantation of MSC improved the neurological symptom in MCA occlusion rat, while, that of MSC transduced HGF gene by HSV vector exhibited more improvement of the symptom in model rat.