Targeted Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells
Targeted Delivery of CX3CL1 to Multiple Lung Tumors by Mesenchymal Stem Cells
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DOI：
10.1634/stemcells.2006-0461
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发表时间：
2007-07
期刊：
影响因子：
5.2
通讯作者：
H. Xin;M. Kanehira;H. Mizuguchi;T. Hayakawa;T. Kikuchi;T. Nukiwa;Y. Saijo
中科院分区：
文献类型：
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作者：
H. Xin;M. Kanehira;H. Mizuguchi;T. Hayakawa;T. Kikuchi;T. Nukiwa;Y. Saijo
MSC是能够分化成各种中胚层型细胞的非造血干细胞。MSC被认为是基于细胞的基因治疗的潜在载体，因为MSC在体外相对容易扩增，并且在全身给药后具有迁移到肿瘤组织并在肿瘤组织中增殖的倾向。在这里，我们证明了小鼠MSC对体外肿瘤细胞的向性和体内静脉注射绿色荧光蛋白阳性MSC后肺中多种肿瘤组织的向性。我们使用腺病毒载体将CX 3CL 1（fractalkine）（一种免疫刺激趋化因子）离体转导至小鼠MSC，所述腺病毒载体在纤维球中具有Arg-Gly-Asp-4C肽。将表达CX 3CL 1的MSC静脉注射到携带C26和B16 F10细胞肺转移的小鼠中，强烈抑制了肺转移的发展，从而延长了这些荷瘤小鼠的生存期。这种抗肿瘤作用取决于先天免疫和获得性免疫。这些结果表明，骨髓间充质干细胞可以作为一种车辆引入生物制剂到多个肺肿瘤组织。
MSCs are nonhematopoietic stem cells capable of differentiating into various mesoderm‐type cells. MSCs have been considered to be a potential vehicle for cell‐based gene therapy because MSCs are relatively easily expanded in vitro and have the propensity to migrate to and proliferate in the tumor tissue after systemic administration. Here, we demonstrated the tropism of mouse MSCs to tumor cells in vitro and multiple tumor tissues in the lung after i.v. injection of green fluorescent protein‐positive MSCs in vivo. We transduced CX3CL1 (fractalkine), an immunostimulatory chemokine, to the mouse MSCs ex vivo using an adenoviral vector with the Arg‐Gly‐Asp‐4C peptide in the fiber knob. Intravenous injection of CX3CL1‐expressing MSCs to the mice bearing lung metastases of C26 and B16F10 cells strongly inhibited the development of lung metastases and thus prolonged the survival of these tumor‐bearing mice. This antitumor effect depended on both innate and adaptive immunity. These results suggest that MSCs can be used as a vehicle for introducing biological agents into multiple lung tumor tissues.