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微流控环境中癌症驱动的免疫细胞动态变化

Cancer-driven dynamics of immune cells in a microfluidic environment.

作者信息

Agliari Elena, Biselli Elena, De Ninno Adele, Schiavoni Giovanna, Gabriele Lucia, Gerardino Anna, Mattei Fabrizio, Barra Adriano, Businaro Luca

机构信息

Dipartimento di Fisica, Sapienza Università di Roma.

UCBM-CNR Joint Lab for Nanotechnologies for the Life Sciences, Università Campus Bio-Medico di Roma, Rome, Italy.

出版信息

Sci Rep. 2014 Oct 16;4:6639. doi: 10.1038/srep06639.

Abstract

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.

摘要

本研究的范围是通过随机过程推断白细胞的迁移能力,以区分免疫细胞针对损伤(即癌症)的自发组织。为此,将选择性缺乏转录因子IRF-8(IRF-8基因敲除;IRF-8 KO)的免疫缺陷小鼠或免疫健全动物(野生型;WT)的脾细胞,交替地置于基于芯片实验室技术开发的特定微流控环境中,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,我们收集了这两种脾细胞运动的数据,并构建了一套完整的可观测指标,概括了这些实验中系统的生物学复杂性。我们得出结论,具有显著的准确性,IRF-8 KO细胞进行纯粹的不相关随机游走,而WT脾细胞能够进行奇异的漂移随机游走,对于整个系统而言,这种随机游走汇聚成直线弹道运动,从而产生高度协调的反应。这些结果可能提供一个有用的系统,用于定量分析实时细胞间相互作用,并预测组织水平上免疫细胞与肿瘤细胞的行为。

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