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A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids

A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydr...

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Published in:PloS one 2016-05, Vol.11 (5), p.e0154610-e0154610
Main Authors: Massai, Diana, Isu, Giuseppe, Madeddu, Denise, Cerino, Giulia, Falco, Angela, Frati, Caterina, Gallo, Diego, Deriu, Marco A, Falvo D'Urso Labate, Giuseppe, Quaini, Federico, Audenino, Alberto, Morbiducci, Umberto
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cited_by cdi_FETCH-LOGICAL-c559t-27426a8d12426d850edb30167f320dda4b2407f7343ce5406088e5d404a2b82e3
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creator Massai, Diana
Isu, Giuseppe
Madeddu, Denise
Cerino, Giulia
Falco, Angela
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Gallo, Diego
Deriu, Marco A
Falvo D'Urso Labate, Giuseppe
Quaini, Federico
Audenino, Alberto
Morbiducci, Umberto
description A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.
doi_str_mv 10.1371/journal.pone.0154610
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subjects Aerospace engineering
Apoptosis
Biological effects
Biology and Life Sciences
Biophysical Phenomena
Bioreactors
Bones
Cancer
Cell culture
Cell Culture Techniques - instrumentation
Cell growth
Cell Line, Tumor
Computational fluid dynamics
Computer Simulation
Deoxyribonucleic acid
DNA
DNA damage
Earth Sciences
Equipment Design
Fluid flow
Humans
Hydrodynamics
Laboratories
Lung carcinoma
Mass transport
Medicine
Microscopy, Electron, Transmission
Models, Biological
Physical Sciences
Process controls
Research and Analysis Methods
Sedimentation & deposition
Shear stress
Shear stresses
Spheroids
Spheroids, Cellular - cytology
Stem cells
Tissue engineering
Tumor Cells, Cultured - cytology
title A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids
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