Department of Neurosurgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
Cancer Lett. 2010 May 28;291(2):256-62. doi: 10.1016/j.canlet.2009.10.020. Epub 2009 Nov 27.
Disseminating disease of high grade gliomas is difficult to treat. We examined the therapeutic effect of intrathecal administration of mesenchymal stem cells transduced with herpes simplex virus-thymidine kinase gene (MSCtk) followed by systemic ganciclovir (GCV) administration in rat experimental leptomeningeal glioma model. First, to examine in vivo bystander effect, rats were intrathecally co-injected with a mixture of MSCtk and C6 cells and then, intraperitoneally administered with GCV or saline for 10days (co-injection model). Next, to examine the therapeutic effect of MSCtk/GCV therapy, MSCtk cells were intrathecally administered 1day after C6 injection and then, GCV or saline was administered (treatment model). GCV administration significantly reduced tumor size on day 14 both in the co-injection model (0.41+/-0.22 vs. 3.10+/-0.97mm(2), p<0.01) and in the treatment model (0.73+/-.29 vs. 2.84+/-0.82mm(2), p<0.01). Survival was also significantly prolonged in GCV group both in the co-injection model (29.2+/-3.3 vs. 18.8+/-0.8days, p<0.001) and in the treatment model (21.5+/-1.5 vs. 17.2+/-0.5days, p<0.001). This study provided a novel treatment strategy for leptomeningeal glioma dissemination using intrathecal MSCtk injection followed by systemic GCV administration.
高级别神经胶质瘤的播散难以治疗。我们研究了单纯疱疹病毒胸苷激酶基因转染的间充质干细胞（MSCtk）鞘内注射联合全身更昔洛韦（GCV）治疗大鼠实验性脑膜胶质瘤模型的疗效。首先，为了检测体内旁观者效应，我们将 MSCtk 和 C6 细胞混合后鞘内注射，然后连续 10 天腹腔内给予 GCV 或生理盐水（共注射模型）。接下来，为了检测 MSCtk/GCV 治疗的疗效，在 C6 注射后第 1 天鞘内注射 MSCtk 细胞，然后给予 GCV 或生理盐水（治疗模型）。GCV 治疗在共注射模型中（0.41+/-0.22 对 3.10+/-0.97mm(2)，p<0.01）和在治疗模型中（0.73+/-0.29 对 2.84+/-0.82mm(2)，p<0.01）均显著降低肿瘤大小。在共注射模型中（29.2+/-3.3 对 18.8+/-0.8 天，p<0.001）和在治疗模型中（21.5+/-1.5 对 17.2+/-0.5 天，p<0.001），GCV 组的存活率也显著延长。本研究为脑膜胶质瘤播散采用鞘内 MSCtk 注射联合全身 GCV 治疗提供了一种新的治疗策略。
