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Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia.
Grist, Samantha M; Nasseri, S Soroush; Laplatine, Loïc; Schmok, Jonathan C; Yao, Dickson; Hua, Jessica; Chrostowski, Lukas; Cheung, Karen C.
Afiliação
  • Grist SM; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada. samantha.grist@alumni.ubc.ca.
  • Nasseri SS; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Laplatine L; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Schmok JC; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Yao D; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Hua J; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Chrostowski L; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.
  • Cheung KC; Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada. kcheung@ece.ubc.ca.
Sci Rep ; 9(1): 17782, 2019 11 28.
Article em En | MEDLINE | ID: mdl-31780697
We demonstrate the application of a microfluidic platform combining spatiotemporal oxygen control and long-term microscopy monitoring to observe tumour spheroid response to hypoxia. The platform is capable of recreating physiologically-relevant low and cycling oxygen levels not attainable in traditional cell culture environments, while image-based monitoring visualizes cell response to these physiologically-relevant conditions. Monitoring spheroid cultures during hypoxic exposure allows us to observe, for the first time, that spheroids swell and shrink in response to time-varying oxygen profiles switching between 0% and 10% O2; this swelling-shrinkage behaviour appears to be driven by swelling of individual cells within the spheroids. We also apply the system to monitoring tumour models during anticancer treatment under varying oxygen conditions. We observe higher uptake of the anticancer agent doxorubicin under a cycling hypoxia profile than under either chronic hypoxia or in vitro normoxia, and the two-photon microscopy monitoring facilitated by our system also allows us to observe heterogeneity in doxorubicin uptake within spheroids at the single-cell level. Combining optical sectioning microscopy with precise spatiotemporal oxygen control and 3D culture opens the door for a wide range of future studies on microenvironmental mechanisms driving cancer progression and resistance to anticancer therapy. These types of studies could facilitate future improvements in cancer diagnostics and treatment.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Técnicas Analíticas Microfluídicas / Hipóxia Tumoral / Neoplasias Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Técnicas Analíticas Microfluídicas / Hipóxia Tumoral / Neoplasias Idioma: En Ano de publicação: 2019 Tipo de documento: Article