Towards personalized medicine: Chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform

Ruppen, Janine; Wildhaber, Franziska Daniela; Strub, Christoph; Hall, Sean; Geiser, Thomas; Schmid, Ralph; Guenat, Olivier Thierry (2015). Towards personalized medicine: Chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform. Lab on a chip, 15(14), pp. 3076-3085. Royal Society of Chemistry 10.1039/C5LC00454C

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Cancer is responsible for millions of deaths worldwide and the variability in disease patterns calls for patient-specific treatment. Therefore, personalized treatment is expected to become a daily routine in prospective clinical tests. In addition to genetic mutation analysis, predictive chemosensitive assays using patient's cells will be carried out as a decision making tool. However, prior to their widespread application in clinics, several challenges linked to the establishment of such assays need to be addressed. To best predict the drug response in a patient, the cellular environment needs to resemble that of the tumor. Furthermore, the formation of homogeneous replicates from a scarce amount of patient's cells is essential to compare the responses under various conditions (compound and concentration). Here, we present a microfluidic device for homogeneous spheroid formation in eight replicates in a perfused microenvironment. Spheroid replicates from either a cell line or primary cells from adenocarcinoma patients were successfully created. To further mimic the tumor microenvironment, spheroid co-culture of primary lung cancer epithelial cells and primary pericytes were tested. A higher chemoresistance in primary co-culture spheroids compared to primary monoculture spheroids was found when both were constantly perfused with cisplatin. This result is thought to be due to the barrier created by the pericytes around the tumor spheroids. Thus, this device can be used for additional chemosensitivity assays (e.g. sequential treatment) of patient material to further approach the personalized oncology field.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine
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 Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Ruppen, Janine; Hall, Sean; Geiser, Thomas; Schmid, Ralph and Guenat, Olivier Thierry

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1473-0197

Publisher:

Royal Society of Chemistry

Language:

English

Submitter:

Olivier Thierry Guenat

Date Deposited:

08 Jul 2015 08:36

Last Modified:

02 Nov 2016 13:37

Publisher DOI:

10.1039/C5LC00454C

PubMed ID:

26088102

BORIS DOI:

10.7892/boris.69319

URI:

https://boris.unibe.ch/id/eprint/69319

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