Microfluidic-enabled self-organized tumor model for in vitro cytotoxicity assessment of doxorubicin
- PDF / 3,030,029 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 61 Downloads / 138 Views
Microfluidic-enabled self-organized tumor model for in vitro cytotoxicity assessment of doxorubicin Yamin Yang 1
&
Sijia Liu 1 & Chunxiao Chen 1 & Haipeng Huang 1 & Ling Tao 1 & Zhiyu Qian 1 & Weitao Li 1
Accepted: 10 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The advent of microfluidic technologies has enabled a better recapitulation of in vitro tumor model with higher biological relevance over conventional monolayer assays. This work built upon a microfluidic system that supported the spontaneous aggregate formation of tumoral cells under flow-induced dynamic physical forces in a confined microchamber without additional matrix materials. Our findings indicated that fluidic streams significantly modulated the biological and architectural features of human breast adenocarcinoma cell (MCF-7), human hepatocarcinoma cell (HepG2), and human cervix adenocarcinoma cell (HeLa) with cell-type-dependent variation. The microfluidic platform was further integrated with a fluorescence detection and imaging system, allowing for non-invasive monitoring of cellular accumulation and spatial distribution of a chemotherapeutic agent, doxorubicin (DOX). The cytotoxic effects of DOX of various concentrations were determined and compared in MCF-7 cells in conventional two-dimensional (2D) static and microfluidic culture conditions. Dose-dependent response to DOX was noticed in both cultures, whereas tumor micronodules grown in microfluidic devices demonstrated significantly lower sensitivity to DOX at increased concentration. Our platform owns promising potentials as a universal modality for bridging traditional 2D cell cultures and in vivo experimentation for preclinical anticancer drug screening. Keywords Tumor-on-chip . Microfluidics . Doxorubicin . In vitro cytotoxicity assessment
1 Introduction In recognition of the limitations of conventional twodimensional (2D) static cell culture platform for recapitulating native tumor biology, innovative three-dimensional (3D) cell culture systems have been developed for better mimicking the physiological complexity of in vivo tumor phenotype and microenvironment (Edmondson et al. 2014; Li and Kumacheva 2018; Monteiro et al. 2020). Recent advances in ex vivo assembly of biomimetic 3D tumor models for anticancer drug screening have been focused on multicellular tumor spheroid Yamin Yang and Sijia Liu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-020-00523-2) contains supplementary material, which is available to authorized users. * Yamin Yang [email protected] 1
Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, 169 Sheng Tai West Road, Nanjing 211106, Jiangsu, China
formation with the assistance of biologically-derived matrix components (e.g. hydrogel, Matrigel) or scaffold (Li and Kumacheva 2018; Monteiro et al. 2020). However, limited throughput, low reproducibility, non-uniform spheroid size, and unmet l
Data Loading...
