Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma.
Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma.
复制标题
内皮祖细胞（EPC）作为人神经胶质瘤大鼠模型的基因载体系统。
DOI：
10.1371/journal.pone.0030310
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Arbab AS
中科院分区：
文献类型：
--
作者：
Varma NR;Janic B;Iskander AS;Shankar A;Bhuiyan MP;Soltanian-Zadeh H;Jiang Q;Barton K;Ali MM;Arbab AS
由于干细胞具有迁移至病变部位的独特性质，因此干细胞被用作向肿瘤，特别是胶质瘤递送治疗基因的载体。追踪移植后所选细胞群的转基因的运动、定位、植入效率和功能能力或表达是至关重要的。本研究的目的是研究1）静脉内施用的遗传转化的脐带血来源的EPCs是否可以将人钠碘同向转运体（hNIS）携带到大鼠原位人脑胶质瘤模型中的肿瘤部位并表达转基因产物，以及2）这些施用的EPCs的积累是否可以通过不同的体内成像方式来跟踪。培养收集的EPCs并转导以携带hNIS。测定细胞活力、微分容量和Tc-99 m摄取。静脉内给予500万至1000万个EPC，并在第8天获得Tc-99-SPECT图像，以确定肿瘤中EPC的积累和转基因的表达（增加Tc-99 m的活性）。免疫组化检测肿瘤组织中内皮细胞标志物和hNIS阳性细胞。转导的EPCs也被磁性标记，并通过MRI和组织化学证实细胞的积聚。SPECT分析显示接受转导的EPCs的肿瘤中Tc-99 m的活性增加，指示转基因（hNIS）的表达。肿瘤中Tc-99 m的活性也依赖于施用的转导的EPCs的数量。MRI显示磁性标记的EPCs聚集。免疫组化显示肿瘤内铁和hNIS阳性，人CD 31和vWF阳性细胞。EPC能够携带和表达hNIS在胶质瘤静脉注射后。SPECT检测EPCs的迁移和hNIS基因的表达。内皮祖细胞可作为基因载体/递送系统用于胶质瘤治疗，也可作为成像探针。
Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities. Collected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors. EPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes.
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影响因子：
2.7
作者：
Rad, Ali M.;Janic, Branislava;Arbab, Ali S.
通讯作者：
Arbab, Ali S.
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
影响因子：
3.1
作者：
Chen, Libo;Altman, Annette;Haberkorn, Uwe
通讯作者：
Haberkorn, Uwe
影响因子：
2.4
作者：
Dickson, Paxton V.;Hamner, John B.;Davidoff, Andrew M.
通讯作者：
Davidoff, Andrew M.
影响因子：
15.9
作者：
Aboody, KS;Najbauer, J;Perides, G
通讯作者：
Perides, G