title: Development and characterization of a microfluidic model of the tumour microenvironment.
abstract: The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and enables modelling and study of the tumour microenvironment in real-time. The versatility of this microfluidic platform allows for different aspects of the microenvironment to be monitored and dissected. This is exemplified here by real-time profiling of oxygen and glucose concentrations inside the device as well as effects on cell proliferation and growth, ROS generation and apoptosis. Heterotypic cell interactions were also studied. The device provides a live 'window' into the microenvironment and could be used to study cancer cells for which it is difficult to generate tumour spheroids. Another major application of the device is the study of effects of the microenvironment on cellular drug responses. Some data is presented for this indicating the device's potential to enable more physiological in vitro drug screening.
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: Jose M
authors: JM
authors: Ayuso
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: María
authors: M
authors: Virumbrales-Muñoz
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: Alodia
authors: A
authors: Lacueva
authors: Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza, Spain.|Dpt. Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain.
authors: Pilar M
authors: PM
authors: Lanuza
authors: Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Bioengineering Institute, University Miguel Hernández, Spain.
authors: Elisa
authors: E
authors: Checa-Chavarria
authors: Instituto de Tecnología Química (Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Científicas), Spain.
authors: Pablo
authors: P
authors: Botella
authors: Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Bioengineering Institute, University Miguel Hernández, Spain.
authors: Eduardo
authors: E
authors: Fernández
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: Manuel
authors: M
authors: Doblare
authors: Department of Biology, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom.
authors: Simon J
authors: SJ
authors: Allison
authors: Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom.
authors: Roger M
authors: RM
authors: Phillips
authors: Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza, Spain.|Dpt. Biochemistry and Molecular and Cell Biology, University of Zaragoza, Zaragoza, Spain.|Dpt. Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Zaragoza, Spain.|Aragón I+D Foundation (ARAID), Government of Aragon, Zaragoza, Spain.
authors: Julián
authors: J
authors: Pardo
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: Luis J
authors: LJ
authors: Fernandez
authors: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Spain.|Aragón Institute of Engineering Research (I3A), University of Zaragoza, Spain.|Aragon Institute of Biomedical Research, Instituto de Salud Carlos III, Spain.
authors: Ignacio
authors: I
authors: Ochoa
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D005947:Glucose / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059008:Time-Lapse Imaging; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D020100:Hydrogels; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D005947:Glucose; D010100:Oxygen