Moore X-L, Lu J, Sun L, Zhu C-J, Tan P, Wong M-C
Brain Tumor Research Lab, Division of Medical Science, National Cancer Center, 11 Medical Drive, Singapore 169610, Singapore.
Gene Ther. 2004 May;11(10):811-8. doi: 10.1038/sj.gt.3302151.
Current treatment of malignant glioma brain tumors is unsatisfactory. Gene therapy has much promise, but target-specific vectors are needed. Endothelial progenitor cells (EPCs) have in vivo homing specificity to angiogenic sites and are thus potential vehicles for site-specific gene therapy. However, reports of EPCs "homing" to intracranial solid tumors are lacking. We investigated EPCs' "homing" specificity using a murine intracranial glioma model. EPCs, derived from human cord blood, were labeled with a fluorogenic agent CFSE and intravenously injected into SCID mice bearing orthotopic gliomas. At 7-14 days after EPC injection, mouse brains and other vital organs were examined for distribution of transplanted EPCs. As controls, CFSE-labeled human umbilical vein endothelial cells (HUVECs) and EPCs were intravenously injected into matched glioma SCID mice (HUVEC control groups) and nontumor SCID mice (nontumor-bearing control groups), respectively. Fluorescence image analysis revealed that systemically transplanted EPCs 'homed' to brain tumors with significantly higher specificity as compared to other organs within the experimental group (P<0.001) and to anatomically matched brain sections from the control groups (P<0.001). Our study demonstrates EPCs' in vivo tropism for intracranial gliomas, with potential for cell delivery of brain tumor spatial-specific gene therapy.
目前恶性胶质瘤脑肿瘤的治疗效果并不理想。基因治疗前景广阔,但需要靶向特异性载体。内皮祖细胞(EPCs)在体内对血管生成部位具有归巢特异性,因此是位点特异性基因治疗的潜在载体。然而,缺乏关于EPCs“归巢”至颅内实体肿瘤的报道。我们使用小鼠颅内胶质瘤模型研究了EPCs的“归巢”特异性。源自人脐带血的EPCs用荧光剂CFSE标记,并静脉注射到携带原位胶质瘤的SCID小鼠体内。在注射EPCs后7 - 14天,检查小鼠脑和其他重要器官中移植EPCs的分布。作为对照,将CFSE标记的人脐静脉内皮细胞(HUVECs)和EPCs分别静脉注射到匹配的胶质瘤SCID小鼠(HUVEC对照组)和非肿瘤SCID小鼠(无肿瘤对照组)体内。荧光图像分析显示,与实验组内的其他器官相比(P<0.001),以及与对照组解剖学匹配的脑切片相比(P<0.001),全身移植的EPCs以显著更高的特异性“归巢”至脑肿瘤。我们的研究证明了EPCs在体内对颅内胶质瘤的嗜性,具有进行脑肿瘤空间特异性基因治疗细胞递送的潜力。