A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids.
This study reports on a microfluidic platform on which single multicellular spheroids from malignant pleural mesothelioma (MPM), an aggressive tumor with poor prognosis, can be loaded, trapped and tested for chemotherapeutic drug response. A new method to detect the spheroid viability cultured on the microfluidic chip as a function of the drug concentration is presented. This approach is based on the evaluation of the caspase activity in the supernatant sampled from the chip and tested using a microplate reader. This simple and time-saving method does only require a minimum amount of manipulations and was established for very low numbers of cells. This feature is particularly important in view of personalised medicine applications for which the number of cells obtained from the patients is low. MPM spheroids were continuously perfused for 48 hours with cisplatin, one of the standard chemotherapeutic drugs used to treat MPM. The 50% growth inhibitory concentration of cisplatin in perfused MPM spheroids was found to be twice as high as in spheroids cultured under static conditions. This chemoresistance increase might be due to the continuous support of nutrients and oxygen to the perfused spheroids.
ARTORG Lung Regeneration Technologies Lab, University of Berne, Murtenstrasse 50, CH-3010 Berne, Switzerland. olivier.guenat@artorg.unibe.ch.
Janine
J
Ruppen
Lourdes
L
Cortes-Dericks
Emanuele
E
Marconi
Golnaz
G
Karoubi
Ralph A
RA
Schmid
Renwang
R
Peng
Thomas M
TM
Marti
Olivier T
OT
Guenat
D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods; D006801:Humans; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism*