Abstract
Metastasis of cancer cells to various organs in the human body is a significant oncological problem. The mechanisms that activate the invasion of cancer cells are not well understood. The research on the processes of cancer invasion is limited under laboratory conditions, because there are still few biotechnological solutions developed to conduct advanced, three-dimensional (3D) cell cultures in vitro. It is necessary to develop new tools for cell engineering that will allow the study of the processes related to cancer metastases and that will enable the analysis of interactions between non-malignant and cancer cells. In this work, a new body-on-a-chip microfluidic system was designed. The microsystem was made of two layers of biocompatible poly(dimethyl siloxane) (PDMS) and a thin, porous PDMS membrane, which was the surface of cell growth. The developed microsystem enabled 3D culture of several types of non-malignant and cancer cells under microfluidic conditions. Four types of cells were cultured simultaneously in the microsystem: non-malignant lung cells (MRC-5), breast fibroblasts (HMF) and co-culture of ovarian fibroblasts (HOF) and ovarian cancer cells (A2780). Additionally, the use of cellular co-culture allowed the imitation of the physiological structure of cancer tissue, composed of a cancerous parenchyma and a non-cancerous stroma. The multi-organ cell culture model was characterized by viability tests: AlamarBlue assay and differential fluorescence staining with propidium iodide and calcein-AM. The changes in the morphology of lung cells and breast fibroblasts because of interaction with ovarian cancer model were also observed using microscopic methods. The cancer cells can create new inflammatory disease outbreaks as a result of interaction with the microenvironment created by non-malignant cells. Therefore, in the next stage of research, the body-on-a-chip system will be used for analyzing the invasion of ovarian cancer cells by monitoring pro-inflammatory factors in the microenvironment created by non-malignant cells of other organs.
Author Contributions
Conceptualization, M.F.; methodology, M.F. and E.J.; validation, M.F. and E.J.; formal analysis, M.F., E.J. and A.D.; investigation, M.F.; resources, A.D.; data curation, M.F.; writing—original draft preparation, M.F.; writing—review and editing, E.J. and A.D.; visualization, M.F.; supervision, E.J. and A.D.; project administration, A.D.; funding acquisition, A.D. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the project: Initiative of Excellence—Research University BIOTECHMED 2, grant number 1820/2/Z01/POB4/2021.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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