Radiation increases invasion of gene-modified mesenchymal stem cells into tumors.
Radiation increases invasion of gene-modified mesenchymal stem cells into tumors.
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DOI：
10.1016/j.ijrobp.2008.06.1953
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发表时间：
2009-11-01
影响因子：
7
通讯作者：
Lawrence, Theodore S.
中科院分区：
文献类型：
--
作者：
Zielske, Steven P.;Livant, Donna L.;Lawrence, Theodore S.
关键词：
间充质干细胞（MSCs）是骨髓中的多能细胞，已被发现可以迁移到肿瘤中，这表明它可能用于癌症基因治疗。间充质干细胞迁移到组织损伤部位，包括受辐射损伤的正常组织。在这项研究中，我们研究肿瘤放射治疗对慢病毒转导的间充质干细胞向肿瘤定位的影响。用亲脂性染料标记间充质干细胞，研究其向结肠癌异种移植物的迁移。随后，用慢病毒载体转导骨髓间充质干细胞来模拟基因治疗并标记注入骨髓间充质干细胞。对LoVo肿瘤异种移植物进行增加剂量的放射治疗，以评估对MSC定位的影响，并通过定量PCR测量。通过侵袭实验测定MSC的侵袭效率。MSCs迁移到各种来源的肿瘤异种移植物中，在正常组织中发现的细胞很少。慢病毒载体有效地转导间充质干细胞存在，而不是不存在，聚苯乙烯。当用增加剂量的辐射治疗LoVo肿瘤时，发现更多的MSCs向LoVo肿瘤迁移，而不是向未治疗的肿瘤迁移。辐照增加了HT-29和MDA-MB-231异种移植物中MSC的定位，但对UMSCC1没有作用。肿瘤中MCP-1的表达与MSC浸润的基础水平无关，然而，MCP-1在辐照肿瘤中适度升高。受照射的LoVo细胞培养基刺激MSC向基底膜的侵袭。这些发现表明，辐射诱导损伤可用于将MSC靶向肿瘤，这可能会提高MSC癌症基因治疗的有效性。肿瘤源性因子的产生对辐射的反应刺激MSC侵袭。
Mesenchymal stem cells (MSCs) are multipotent cells in the bone marrow which have been found to migrate to tumors, suggesting a potential use for cancer gene therapy. MSCs migrate to sites of tissue damage, including normal tissues damaged by radiation. In this study, we investigate the effect of tumor radiation therapy on localization of lentivirus-transduced MSCs to tumors. MSCs were labeled with a lipophilic dye to investigate migration to colon cancer xenografts. Subsequently, MSCs were transduced with a lentiviral vector to model gene therapy and mark infused MSCs. LoVo tumor xenografts were treated with increasing doses of radiation therapy to assess the effect on MSC localization, which was measured by quantitative PCR. MSC invasion efficiency was determined in an invasion assay. MSCs migrated to tumor xenografts of various origins, with few cells found in normal tissues. A lentiviral vector efficiently transduced MSCs in the presence, but not absence, of Polybrene. When LoVo tumors were treated with increasing doses of radiation, more MSCs were found to migrate to them than to untreated tumors. Irradiation increased MSC localization in HT-29 and MDA-MB-231, but not UMSCC1, xenografts. MCP-1 expression in tumors did not correlate with basal levels of MSC infiltration, however, MCP-1 was modestly elevated in irradiated tumors. Media from irradiated LoVo cells stimulated MSC invasion into basement membranes. These findings suggest that radiation induced injury can be used to target MSCs to tumors, which may increase the effectiveness of MSC cancer gene therapy. Production of tumor-derived factors in response to radiation stimulates MSC invasion.
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影响因子：
11.2
作者：
Nakamizo, A;Marini, F;Lang, FF
通讯作者：
Lang, FF
影响因子：
2.6
作者：
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通讯作者：
Vacek, A
DOI：
10.1016/j.bbrc.2005.06.116
发表时间：
2005-08-26
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
3.6
作者：
vanValen, F;KentrupLardong, V;Jurgens, H
通讯作者：
Jurgens, H
影响因子：
3.5
作者：
Chapel, A;Bertho, JM;Thierry, D
通讯作者：
Thierry, D