Development and characterization of a microfluidic model of the tumour microenvironment
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,...
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| Published in | Scientific reports Vol. 6; no. 1; p. 36086 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
31.10.2016
Nature Publishing Group |
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| Online Access | Get full text |
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| 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. |
|---|---|
| AbstractList | 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. 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.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. 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. |
| ArticleNumber | 36086 |
| Author | Checa-Chavarria, Elisa Lacueva, Alodia Doblare, Manuel Allison, Simon J. Ochoa, Ignacio Virumbrales-Muñoz, María Pardo, Julián Phillips, Roger M. Fernandez, Luis J. Lanuza, Pilar M. Fernández, Eduardo Ayuso, Jose M. Botella, Pablo |
| Author_xml | – sequence: 1 givenname: Jose M. surname: Ayuso fullname: Ayuso, Jose M. organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III – sequence: 2 givenname: María surname: Virumbrales-Muñoz fullname: Virumbrales-Muñoz, María organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III – sequence: 3 givenname: Alodia surname: Lacueva fullname: Lacueva, Alodia organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III – sequence: 4 givenname: Pilar M. surname: Lanuza fullname: Lanuza, Pilar M. organization: Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Dpt. Biochemistry and Molecular and Cell Biology, University of Zaragoza – sequence: 5 givenname: Elisa surname: Checa-Chavarria fullname: Checa-Chavarria, Elisa organization: Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Bioengineering Institute, University Miguel Hernández – sequence: 6 givenname: Pablo surname: Botella fullname: Botella, Pablo organization: Instituto de Tecnología Química (Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Científicas) – sequence: 7 givenname: Eduardo surname: Fernández fullname: Fernández, Eduardo organization: Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Bioengineering Institute, University Miguel Hernández – sequence: 8 givenname: Manuel surname: Doblare fullname: Doblare, Manuel organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III – sequence: 9 givenname: Simon J. surname: Allison fullname: Allison, Simon J. organization: Department of Biology, University of Huddersfield – sequence: 10 givenname: Roger M. surname: Phillips fullname: Phillips, Roger M. organization: Department of Pharmacy, University of Huddersfield – sequence: 11 givenname: Julián surname: Pardo fullname: Pardo, Julián organization: Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Dpt. Biochemistry and Molecular and Cell Biology, University of Zaragoza, Dpt. Microbiology, Preventive Medicine and Public Health, University of Zaragoza, Aragón I+D Foundation (ARAID), Government of Aragon – sequence: 12 givenname: Luis J. surname: Fernandez fullname: Fernandez, Luis J. organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III – sequence: 13 givenname: Ignacio surname: Ochoa fullname: Ochoa, Ignacio organization: Group of Structural Mechanics and Materials Modelling (GEMM), Centro Investigacion Biomedica en Red. Bioingenieria, biomateriales y nanomedicina (CIBER-BBN), Aragón Institute of Engineering Research (I3A), University of Zaragoza, Aragon Institute of Biomedical Research, Instituto de Salud Carlos III |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27796335$$D View this record in MEDLINE/PubMed |
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| Title | Development and characterization of a microfluidic model of the tumour microenvironment |
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