title: Towards personalized medicine: chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform.
abstract: 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.
authors.affiliation: ARTORG Lung Regeneration Technologies Lab, University of Bern, Murtenstrasse 50, CH-3010 Bern, Switzerland. olivier.guenat@artorg.unibe.ch.
authors.forename: Janine
authors.initials: J
authors.lastname: Ruppen
authors.forename: Franziska D
authors.initials: FD
authors.lastname: Wildhaber
authors.forename: Christoph
authors.initials: C
authors.lastname: Strub
authors.forename: Sean R R
authors.initials: SR
authors.lastname: Hall
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Schmid
authors.forename: Thomas
authors.initials: T
authors.lastname: Geiser
authors.forename: Olivier T
authors.initials: OT
authors.lastname: Guenat
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000295:instrumentation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D018920:Coculture Techniques; D004867:Equipment Design; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D057285:Precision Medicine; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin