In vitro lung cancer multicellular tumor spheroid formation using a microfluidic device

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Microfluidics

Background:

• The in vivo tumor microenvironment (TME) is complex and challenging to replicate in vitro.
• Multicellular tumor spheroids (MCTSs) offer a more physiologically relevant model than 2D cultures.
• Microfluidic systems enable precise control over the microenvironment for spheroid studies.

Purpose of the Study:

• To demonstrate self-organizing MCTS formation within a microfluidic system.
• To investigate MCTS behavior under controlled nutrient and oxygen gradients.
• To assess the impact of a matrix metalloproteinase (MMP) inhibitor on MCTS stability.

Main Methods:

• Engineered a microfluidic device to generate nutrient and oxygen gradients.
• Formed MCTSs using cancer cells, vascular endothelial cells, and collagen matrix.
• Utilized a passive fluidic pump for continuous cell culture medium perfusion.
• Administered an MMP inhibitor to evaluate its effect on the collagen matrix.

Main Results:

• Continuous medium perfusion is critical for successful MCTS formation and stability.
• Perfusion influenced cancer cell proliferation and endothelial cell layer integrity.
• MMP inhibitor addition stabilized the collagen matrix, preventing shrinkage and detachment.
• The microfluidic system facilitated long-term observation of MCTS development and drug response.

Conclusions:

• The constant flow microfluidic system is advantageous for long-term MCTS observation and studying tumor development.
• Microfluidic MCTS formation is a potent tool for drug screening, tumorigenesis, and metastasis research.
• Controlled microenvironment in microfluidics enhances the in vitro tumor model's relevance.