Organs on chip approach: a tool to evaluate cancer -immune cells interactions.
Organs on chip approach: a tool to evaluate cancer -immune cells interactions.
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DOI：
10.1038/s41598-017-13070-3
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发表时间：
2017-10-06
影响因子：
4.6
通讯作者：
Businaro L
中科院分区：
文献类型：
--
作者：
Biselli E;Agliari E;Barra A;Bertani FR;Gerardino A;De Ninno A;Mencattini A;Di Giuseppe D;Mattei F;Schiavoni G;Lucarini V;Vacchelli E;Kroemer G;Di Natale C;Martinelli E;Businaro L
在本文中，我们讨论了数值描述符和统计物理概念的适用性，以表征在微观水平上观察到的复杂的生物系统，通过器官芯片的方法。为此，我们采用在微流体平台上收集的数据，在该平台中，白细胞可以通过适当构建的通道朝向其目标移动。通过标准时间推移成像记录白细胞行为。特别是，我们分析了三组人外周血单核细胞（PBMC）：杂合突变体（其中只有一个拷贝的FPR 1基因是正常的），纯合突变体（其中编码FPR 1的两个等位基因都是功能丧失的变体）和来自“野生型”供体的细胞（FPR 1表达正常）。我们表征了这些细胞的迁移，定量证实了FPR 1在癌症化疗反应中的重要作用。事实上，野生型PBMC对化疗处理的癌细胞进行偏向性随机游走，与它们建立持久的相互作用。相反，杂合突变体在运动中表现出较弱的偏向性，而纯合突变体则表现出相当不相关的随机游走，两者都无法与它们的靶点接触。接下来，我们专注于野生型细胞和研究白细胞与癌细胞的相互作用，开发一种新的启发式程序，在动力系统中的李雅普诺夫稳定性的启发。
In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a microfluidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from ‘wild type’ donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative confirmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems.
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影响因子：
20.1
作者：
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通讯作者：
Aird WC
DOI：
10.1073/pnas.1001705107
发表时间：
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影响因子：
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作者：
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