Varma Nadimpalli Ravi S, Barton Kenneth N, Janic Branislava, Shankar Adarsh, Iskander Asm, Ali Meser M, Arbab Ali S
Nadimpalli Ravi S Varma, Branislava Janic, Adarsh Shankar, ASM Iskander, Meser M Ali, Ali S Arbab, Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, MI 48202, United States.
World J Clin Oncol. 2013 Nov 10;4(4):91-101. doi: 10.5306/wjco.v4.i4.91.
To determine whether endothelial progenitor cells (EPCs) can be used as delivery vehicle for adenoviral vectors and imaging probes for gene therapy in glioblastoma.
To use cord blood derived EPCs as delivery vehicle for adenoviral vectors and imaging probes for glioma gene therapy, a rat model of human glioma was made by implanting U251 cells orthotopically. EPCs were transfected with an adenovirus (AD5/carrying hNIS gene) and labeled with iron oxide and inoculated them directly into the tumor 14 d following implantation of U251 cells. Magnetic resonance imaging (MRI) was used to in vivo track the migration of EPCs in the tumor. The expression of gene products was determined by in vivo Tc-99m single photon emission computed tomography (SPECT). The findings were validated with immunohistochemistry (IHC).
EPCs were successfully transfected with the adenoviral vectors carrying hNIS which was proved by significantly (P < 0.05) higher uptake of Tc-99m in transfected cells. Viability of EPCs following transfection and iron labeling was not altered. In vivo imaging showed the presence of iron positive cells and the expression of transgene (hNIS) product on MRI and SPECT, respectively, all over the tumors following administration of transfected and iron labeled EPCs in the tumors. IHC confirmed the distribution of EPC around the tumor away from the injection site and also showed transgene expression in the tumor. The results indicated the EPCs' ability to deliver adenoviral vectors into the glioma upon intratumor injection.
EPCs can be used as vehicle to deliver adenoviral vector to glioma and also act as imaging probe at the same time.
确定内皮祖细胞（EPCs）是否可作为腺病毒载体的递送载体以及胶质母细胞瘤基因治疗的成像探针。
为了将脐带血来源的EPCs用作腺病毒载体的递送载体和胶质瘤基因治疗的成像探针，通过原位植入U251细胞建立了人胶质瘤大鼠模型。用携带hNIS基因的腺病毒（AD5）转染EPCs，并用氧化铁标记，在植入U251细胞14天后将其直接接种到肿瘤中。采用磁共振成像（MRI）在体内追踪EPCs在肿瘤中的迁移。通过体内锝-99m单光子发射计算机断层扫描（SPECT）测定基因产物的表达。研究结果通过免疫组织化学（IHC）进行验证。
携带hNIS的腺病毒载体成功转染了EPCs，转染细胞中锝-99m的摄取显著更高（P<0.05），证明了这一点。转染和铁标记后EPCs的活力未改变。体内成像显示，在肿瘤中注射转染并铁标记的EPCs后，肿瘤各处分别在MRI和SPECT上出现铁阳性细胞和转基因（hNIS）产物的表达。IHC证实EPCs分布在远离注射部位的肿瘤周围，并且在肿瘤中也显示出转基因表达。结果表明EPCs在瘤内注射后能够将腺病毒载体递送至胶质瘤。
EPCs可作为载体将腺病毒载体递送至胶质瘤，同时还可作为成像探针。
