Empirical chemosensitivity testing in a spheroid model of ovarian cancer using a microfluidics-based multiplex platform.

Das, Tamal; Meunier, Liliane; Barbe, Laurent; Provencher, Diane; Guenat, Olivier Thierry; Gervais, Thomas; Mes-Masson, Anne-Marie (2013). Empirical chemosensitivity testing in a spheroid model of ovarian cancer using a microfluidics-based multiplex platform. Biomicrofluidics, 7(1), p. 11805. American Insitute of Physics 10.1063/1.4774309

[img]
Preview
Text
BioMicrofluidics 2013 Tamal Das.pdf - Published Version
Available under License Publisher holds Copyright.

Download (2MB) | Preview

The use of biomarkers to infer drug response in patients is being actively pursued, yet significant challenges with this approach, including the complicated interconnection of pathways, have limited its application. Direct empirical testing of tumor sensitivity would arguably provide a more reliable predictive value, although it has garnered little attention largely due to the technical difficulties associated with this approach. We hypothesize that the application of recently developed microtechnologies, coupled to more complex 3-dimensional cell cultures, could provide a model to address some of these issues. As a proof of concept, we developed a microfluidic device where spheroids of the serous epithelial ovarian cancer cell line TOV112D are entrapped and assayed for their chemoresponse to carboplatin and paclitaxel, two therapeutic agents routinely used for the treatment of ovarian cancer. In order to index the chemoresponse, we analyzed the spatiotemporal evolution of the mortality fraction, as judged by vital dyes and confocal microscopy, within spheroids subjected to different drug concentrations and treatment durations inside the microfluidic device. To reflect microenvironment effects, we tested the effect of exogenous extracellular matrix and serum supplementation during spheroid formation on their chemotherapeutic response. Spheroids displayed augmented chemoresistance in comparison to monolayer culturing. This resistance was further increased by the simultaneous presence of both extracellular matrix and high serum concentration during spheroid formation. Following exposure to chemotherapeutics, cell death profiles were not uniform throughout the spheroid. The highest cell death fraction was found at the center of the spheroid and the lowest at the periphery. Collectively, the results demonstrate the validity of the approach, and provide the basis for further investigation of chemotherapeutic responses in ovarian cancer using microfluidics technology. In the future, such microdevices could provide the framework to assay drug sensitivity in a timeframe suitable for clinical decision making.

Item Type:

Journal Article (Original Article)

Division/Institute:

10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Lung Regeneration Technologies
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Guenat, Olivier Thierry

Subjects:

600 Technology > 610 Medicine & health
500 Science
500 Science > 570 Life sciences; biology
600 Technology > 620 Engineering

ISSN:

1932-1058

Publisher:

American Insitute of Physics

Language:

English

Submitter:

Olivier Thierry Guenat

Date Deposited:

12 Jun 2014 12:53

Last Modified:

15 Sep 2017 06:33

Publisher DOI:

10.1063/1.4774309

PubMed ID:

24403987

BORIS DOI:

10.7892/boris.46173

URI:

https://boris.unibe.ch/id/eprint/46173

Actions (login required)

Edit item Edit item
Provide Feedback