Cancer-driven dynamics of immune cells in a microfluidic environment.
Cancer-driven dynamics of immune cells in a microfluidic environment.
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DOI：
10.1038/srep06639
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发表时间：
2014-10-16
影响因子：
4.6
通讯作者：
Businaro L
中科院分区：
文献类型：
--
作者：
Agliari E;Biselli E;De Ninno A;Schiavoni G;Gabriele L;Gerardino A;Mattei F;Barra A;Businaro L
目前的工作范围是通过随机过程来推断白细胞的迁移能力，以便区分免疫细胞针对一种侮辱(即癌症)的自发组织。为此，来自免疫缺陷小鼠的脾细胞，选择性地缺乏转录因子IRF-8(IRF-8基因敲除；IRF-8 KO)，或来自免疫活性动物(野生型；WT)的脾细胞，被允许在基于LabOnChip技术开发的特别微流控环境中与小鼠B16.F10黑色素瘤细胞相互作用。在这种情况下，只有WT脾细胞能够与黑色素瘤细胞建立物理相互作用。相反，IRF-8 KO免疫细胞对肿瘤细胞表现出较差的动态反应性。在本研究中，我们收集了这两种类型的脾细胞的运动性数据，并建立了一套完整的观测数据，概括了这些实验中系统的生物学复杂性。以惊人的准确性，我们得出结论，IRF-8 KO细胞执行的是纯粹的不相关的随机行走，而WT脾细胞能够进行奇异的漂移随机行走，这种随机行走在整个系统中以直线弹道运动的方式崩溃，因此产生了高度协调的反应。这些结果可能为定量分析细胞与细胞之间的实时相互作用以及在组织水平上预测免疫细胞与肿瘤细胞的行为提供有用的系统。
Scope of the present work is to infer the migratory ability of leukocytes by stochastic processes in order to distinguish the spontaneous organization of immune cells against an insult (namely cancer). For this purpose, spleen cells from immunodeficient mice, selectively lacking the transcription factor IRF-8 (IRF-8 knockout; IRF-8 KO), or from immunocompetent animals (wild-type; WT), were allowed to interact, alternatively, with murine B16.F10 melanoma cells in an ad hoc microfluidic environment developed on a LabOnChip technology. In this setting, only WT spleen cells were able to establish physical interactions with melanoma cells. Conversely, IRF-8 KO immune cells exhibited poor dynamical reactivity towards the neoplastic cells. In the present study, we collected data on the motility of these two types of spleen cells and built a complete set of observables that recapitulate the biological complexity of the system in these experiments. With remarkable accuracy, we concluded that the IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks that collapsed on a straight ballistic motion for the system as a whole, hence giving rise to a highly coordinate response. These results may provide a useful system to quantitatively analyse the real time cell-cell interactions and to foresee the behavior of immune cells with tumor cells at the tissue level.