Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth.
Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth.
复制标题
DOI：
10.1186/1741-7015-11-139
复制
发表时间：
2013-05-28
期刊：
影响因子：
9.3
通讯作者：
Martin-Duque P
中科院分区：
文献类型：
--
作者：
Belmar-Lopez C;Mendoza G;Oberg D;Burnet J;Simon C;Cervello I;Iglesias M;Ramirez JC;Lopez-Larrubia P;Quintanilla M;Martin-Duque P
间充质干细胞(MSCs)是一种很有吸引力的细胞载体，能够进入肿瘤部位并分泌细胞因子，是一种很有吸引力的抗肿瘤药物载体。多个分离的群体被描述为间充质干细胞，但尽管在体外进行了广泛的表征，但对它们在体内的行为知之甚少。本研究的目的是研究来自五个不同来源(骨髓、脂肪组织、上皮子宫内膜、间质子宫内膜和羊膜)的不同MSC谱系的疗效和效率，以评估它们是否适合基于细胞的抗肿瘤治疗。我们的研究显示了理解MSCs和肿瘤细胞之间相互作用的关键重要性，并提供了信息和方法学途径，可用于开发更安全和更准确的靶向治疗应用。我们首先用两种成像技术测量了不同MSCs在体内的迁移能力和对肿瘤生长的影响：(I)使用人钠碘转运蛋白基因(HNIS)的单光子发射计算机断层扫描(SPECT-CT)和(Ii)使用超顺磁性氧化铁进行磁共振成像。然后，我们寻找这些参数与多能性相关或迁移相关基因表达之间的相关性。我们的结果表明，人骨髓来源的MSCs的迁移明显减少和缓慢，与其他MSCs和人诱导的多能干细胞(HiPSCs)相比也是如此。QPCR数据清楚地表明，MSCs和hiPSCs发挥着非常不同的多能性模式，这与它们在植入能力上的差异以及它们对肿瘤生长的影响有关。这项研究揭示了MSC向肿瘤部位募集/迁移的不同及其对肿瘤生长的相应影响。突出的三个观察结果：1)干细胞的跟踪对于检查细胞治疗的安全性和有效性至关重要；2)细胞治疗中使用的MSC谱系需要谨慎选择，以平衡对特定肿瘤类型的疗效和安全性；以及3)不同的多能性和移动模式可能与MSCs的植入能力有关，并且应该作为谱系的临床特征的一部分进行检查。
Mesenchymal stem cells (MSCs) have been promoted as an attractive option to use as cellular delivery vehicles to carry anti-tumor agents, owing to their ability to home into tumor sites and secrete cytokines. Multiple isolated populations have been described as MSCs, but despite extensive in vitro characterization, little is known about their in vivo behavior. The aim of this study was to investigate the efficacy and efficiency of different MSC lineages derived from five different sources (bone marrow, adipose tissue, epithelial endometrium, stroma endometrium, and amniotic membrane), in order to assess their adequacy for cell-based anti-tumor therapies. Our study shows the crucial importance of understanding the interaction between MSCs and tumor cells, and provides both information and a methodological approach, which could be used to develop safer and more accurate targeted therapeutic applications. We first measured the in vivo migration capacity and effect on tumor growth of the different MSCs using two imaging techniques: (i) single-photon emission computed tomography combined with computed tomography (SPECT-CT), using the human sodium iodine symporter gene (hNIS) and (ii) magnetic resonance imaging using superparamagnetic iron oxide. We then sought correlations between these parameters and expression of pluripotency-related or migration-related genes. Our results show that migration of human bone marrow-derived MSCs was significantly reduced and slower than that obtained with the other MSCs assayed and also with human induced pluripotent stem cells (hiPSCs). The qPCR data clearly show that MSCs and hiPSCs exert a very different pluripotency pattern, which correlates with the differences observed in their engraftment capacity and with their effects on tumor growth. This study reveals differences in MSC recruitment/migration toward the tumor site and the corresponding effects on tumor growth. Three observations stand out: 1) tracking of the stem cell is essential to check the safety and efficacy of cell therapies; 2) the MSC lineage to be used in the cell therapy needs to be carefully chosen to balance efficacy and safety for a particular tumor type; and 3) different pluripotency and mobility patterns can be linked to the engraftment capacity of the MSCs, and should be checked as part of the clinical characterization of the lineage.
登录
查看更多内容
影响因子：
3.6
作者：
Gargett, Caroline E.;Schwab, Kjiana E.;Wu, Di
通讯作者：
Wu, Di
影响因子：
5.1
作者：
通讯作者：
--
影响因子：
6.4
作者：
Kang, N-H;Hwang, K-A;Choi, K-C
通讯作者：
Choi, K-C
影响因子：
5.2
作者：
in't Anker, PS;Scherjon, SA;Kanhai, HHH
通讯作者：
Kanhai, HHH
影响因子：
5.2
作者：
Honczarenko, Marek;Le, Yi;Silberstein, Leslie E.
通讯作者：
Silberstein, Leslie E.