Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors.
Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors.
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间充质干细胞作为 CRAd 递送至肿瘤的载体和放大器
DOI：
10.1186/1476-4598-10-134
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发表时间：
2011-11-03
期刊：
影响因子：
37.3
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Xia X;Ji T;Chen P;Li X;Fang Y;Gao Q;Liao S;You L;Xu H;Ma Q;Wu P;Hu W;Wu M;Cao L;Li K;Weng Y;Han Z;Wei J;Liu R;Wang S;Xu G;Wang D;Zhou J;Ma D
背景间充质干细胞（mesenchymal stem cells，MSCs）是治疗多种肿瘤的理想载体。本研究旨在探讨E1 A突变型条件复制型腺病毒Adv-Stat 3（-）在乳腺癌和黑色素瘤细胞中的分布、腺病毒的动力学释放和MSC负载的治疗效果。TCID 50测定和定量PCR。采用transwell平板共培养系统，检测携带Adv-Stat 3（-）的MSCs对乳腺癌和黑色素瘤的体外杀伤能力。普鲁士蓝染色和免疫荧光法检测MSC的肿瘤嗜性。结果Adv Stat 3（-）在MSCs中扩增，感染后4d可释放出Adv Stat 3（-）。携带Adv-Stat 3（-）的MSC引起病毒扩增、Stat 3及其下游蛋白的耗尽，并导致乳腺癌和黑色素瘤细胞系的显著凋亡。体内实验证实了尾静脉注射后24小时MSC优先定位于肿瘤周围，并且在72小时后主要在肿瘤实质中检测到这种定位。静脉注射携带Adv-Stat 3（-）的MSC抑制了Stat 3通路，下调了Ki 67的表达，并在局部肿瘤中招募了CD 11b阳性细胞，抑制肿瘤生长并提高荷瘤小鼠的生存率。结论这些结果表明MSC在一定时间内迁移到肿瘤部位-CRAd是一种靶向递送CRAd并增强肿瘤杀伤效应的有效平台。
BackgroundMesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells.MethodsWe assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID50assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods.ResultsAdv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice.ConclusionsThese results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.
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淋巴瘤内皮优先表达 Tim-3 并通过介导免疫逃避促进淋巴瘤的进展
DOI：
10.1084/jem.20090397
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang X;Bai X;Cao Y;Wu J;Huang M;Tang D;Tao S;Zhu T;Liu Y;Yang Y;Zhou X;Zhao Y;Wu M;Wei J;Wang D;Xu G;Wang S;Ma D;Zhou J
通讯作者：
Zhou J
影响因子：
11.2
作者：
Loebinger MR;Eddaoudi A;Davies D;Janes SM
通讯作者：
Janes SM
影响因子：
82.9
作者：
Heise, C;Hermiston, T;Kirn, D
通讯作者：
Kirn, D
影响因子：
12.4
作者：
Kreppel, F;Gackowski, J;Kochanek, S
通讯作者：
Kochanek, S
影响因子：
5.4
作者：
Kühnel, F;Schulte, B;Kubicka, S
通讯作者：
Kubicka, S