Organs on chip approach: A tool to evaluate cancer-immune cells interactions

Elena Biselli, Elena Agliari, Adriano Barra, Francesca Romana Bertani, Annamaria Gerardino, Adele De Ninno, Arianna Mencattini, Davide Di Giuseppe, Fabrizio Mattei, Giovanna Schiavoni, Valeria Lucarini, Erika Vacchelli, Guido Kroemer, Corrado Di Natale, Eugenio Martinelli, Luca Businaro

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Abstract

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.

Original languageEnglish
Article number12737
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

ASJC Scopus subject areas

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    Biselli, E., Agliari, E., Barra, A., Bertani, F. R., 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. (2017). Organs on chip approach: A tool to evaluate cancer-immune cells interactions. Scientific Reports, 7(1), [12737]. https://doi.org/10.1038/s41598-017-13070-3