Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model

María Virumbrales-Munoz, Jose Maria Ayuso, Marta Olave, Rosa Monge, Diego de Miguel, Luis Martinez-Lostao, Severine le Gac, Manuel Doblare, Ignacio Ochoa, Luis J. Fernandez

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    Abstract

    The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.
    Original languageEnglish
    Article number11998
    Number of pages15
    JournalScientific reports
    Volume7
    DOIs
    Publication statusPublished - 20 Sep 2017

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    Lab-On-A-Chip Devices
    Capillary Action
    Preclinical Drug Evaluations
    Coculture Techniques
    Endothelium
    TNF-Related Apoptosis-Inducing Ligand
    Neoplasms
    Unilamellar Liposomes
    Tumor Microenvironment
    Oxygen
    Essential Drugs
    Food
    Equipment and Supplies
    Drug Compounding
    Drug Resistance
    Cell Culture Techniques
    Cell Proliferation
    Breast Neoplasms

    Keywords

    • microfluidics, tumor on a chip, 3D models, endothelium, drug delivery

    Cite this

    Virumbrales-Munoz, M., Ayuso, J. M., Olave, M., Monge, R., de Miguel, D., Martinez-Lostao, L., ... Fernandez, L. J. (2017). Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model. Scientific reports, 7, [11998]. https://doi.org/10.1038/s41598-017-12049-4
    Virumbrales-Munoz, María ; Ayuso, Jose Maria ; Olave, Marta ; Monge, Rosa ; de Miguel, Diego ; Martinez-Lostao, Luis ; le Gac, Severine ; Doblare, Manuel ; Ochoa, Ignacio ; Fernandez, Luis J. / Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model. In: Scientific reports. 2017 ; Vol. 7.
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    abstract = "The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.",
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    author = "Mar{\'i}a Virumbrales-Munoz and Ayuso, {Jose Maria} and Marta Olave and Rosa Monge and {de Miguel}, Diego and Luis Martinez-Lostao and {le Gac}, Severine and Manuel Doblare and Ignacio Ochoa and Fernandez, {Luis J.}",
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    Virumbrales-Munoz, M, Ayuso, JM, Olave, M, Monge, R, de Miguel, D, Martinez-Lostao, L, le Gac, S, Doblare, M, Ochoa, I & Fernandez, LJ 2017, 'Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model', Scientific reports, vol. 7, 11998. https://doi.org/10.1038/s41598-017-12049-4

    Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model. / Virumbrales-Munoz, María; Ayuso, Jose Maria; Olave, Marta; Monge, Rosa; de Miguel, Diego; Martinez-Lostao, Luis; le Gac, Severine ; Doblare, Manuel; Ochoa, Ignacio; Fernandez, Luis J.

    In: Scientific reports, Vol. 7, 11998, 20.09.2017.

    Research output: Contribution to journalArticleProfessional

    TY - JOUR

    T1 - Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture model

    AU - Virumbrales-Munoz, María

    AU - Ayuso, Jose Maria

    AU - Olave, Marta

    AU - Monge, Rosa

    AU - de Miguel, Diego

    AU - Martinez-Lostao, Luis

    AU - le Gac, Severine

    AU - Doblare, Manuel

    AU - Ochoa, Ignacio

    AU - Fernandez, Luis J.

    PY - 2017/9/20

    Y1 - 2017/9/20

    N2 - The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.

    AB - The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the tumour model exhibited in vivo features, e.g., oxygen gradients and preferential proliferation of cells with better access to nutrients and oxygen. Next, we observed the endothelium structure lost its integrity in the co-culture. Following this, we evaluated two drug formulations of TRAIL (TNF-related apoptosis inducing ligand): soluble and anchored to a LUV (large unilamellar vesicle). Both diffused through the endothelium, LUV-TRAIL being more efficient in killing tumour cells, showing no effect on the integrity of endothelium. Overall, we have developed a simple capillary force-based microfluidic device for 2D and 3D cell co-cultures. Our device allows high-throughput approaches, patterning different cell types and generating gradients without specialised equipment. We anticipate this microfluidic device will facilitate drug screening in a relevant microenvironment thanks to its simple, effective and user-friendly operation.

    KW - microfluidics, tumor on a chip, 3D models, endothelium, drug delivery

    U2 - 10.1038/s41598-017-12049-4

    DO - 10.1038/s41598-017-12049-4

    M3 - Article

    VL - 7

    JO - Scientific reports

    JF - Scientific reports

    SN - 2045-2322

    M1 - 11998

    ER -