Long-term three-dimensional cell culture and anticancer drug activity evaluation in a microfluidic chip
Karina Kwapiszewska , Agnieszka Stelmachowska , Radosław Kwapiszewski , Michał Chudy , Artur Dybko , Zbigniew Brzózka
AbstractIn this work, we present a microfluidic array of microwells for long-term tumor spheroid cultivation and anticancer drug activity evaluation. The three-dimensional microfluidic system was obtained by double casting of poly(dimethylsiloxane). Spheroids of HT-29 human carcinoma cells were cultured in the microsystem for four weeks. After two weeks of the culture growth slowdown and stop were observed and high cell viability was determined within next two weeks. The characteristics of a homeostasis-like state were achieved. A cytostatic drug (5-fluorouracil) was introduced into the microsystem with different frequency (every day or every second day) and different concentrations. The geometry and construction of the microsystem enables flushing away of unaggregated (including dead) cells while viable spheroids remain inside microwells and decreasing spheroid diameter can be observed and measured as an indicator of decreasing cell viability. The results have shown differences in response of spheroids to different concentrations of 5-fluorouracil. It was also observed, that higher frequency of drug dosing resulted in more rapid spheroid diameter decrease. The presented microfluidic system is a solution for cell-based studies in an in vivo-like microfluidic environment. Moreover, observation of decreasing spheroid dimensions is a low-cost, label-free and easy-to-conduct mean of a quantitative determination of a 3D cellular model response to a applied drug. It is suitable for long-term observation of spheroid response, in a contrary to other viability assays requiring termination of a culture.
|Journal series||Biosensors & Bioelectronics, ISSN 0956-5663|
|Publication size in sheets||0.5|
|Keywords in English||Anticancer drugs, Long-term cell culture, Microfluidics, Repeated doses, Three-dimensional cell culture, Tumor spheroid|
|ASJC Classification||; ; ; ;|
|Score|| = 40.0, 08-01-2020, ArticleFromJournal|
= 40.0, 08-01-2020, ArticleFromJournal
|Publication indicators||= 50; = 23.0; : 2013 = 1.718; : 2013 = 6.451 (2) - 2013=6.054 (5)|
|Citation count*||23 (2015-05-30)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.