On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing

Area of Science:

• Biomedical Engineering
• Cancer Research
• Microfluidics

Background:

• Organoid models are crucial for evaluating drug toxicity in cancer research.
• Standardized organoid size and structure are essential for reliable drug testing.
• Microfluidics provides controlled, contamination-free environments for biomedical research.

Purpose of the Study:

• To design and fabricate low-cost microfluidic devices for renal cancer organoid development.
• To create size-controllable organoids within alginate hydrogels for drug testing.
• To assess the efficacy of chemotherapeutic agents and analyze tumor microenvironment responses.

Main Methods:

• Fabrication of simple, low-cost microfluidic devices.
• Encapsulation of Caki human renal cancer cells and mesenchymal stem cells in alginate hydrogels.
• Culturing of uniform-sized alginate capsules for 21 days to form organoids.
• Assessment of organoid development using calcein staining and MTT assay.
• Analysis of HIF-1α, CXCR4, and CXCL-12 protein and gene expression.

Main Results:

• Successfully formed size-controllable renal cancer organoids within alginate hydrogels using microfluidics.
• Observed organoid development and sphere structure changes over time.
• Demonstrated the ability to measure drug effects (cisplatin) on organoids.
• Evaluated changes in HIF-1α, CXCR4, and CXCL-12 levels in response to cisplatin.

Conclusions:

• Standardized renal cancer organoids can be reliably generated using a lab-on-a-chip microfluidic system.
• This organoid model is effective for measuring drug effects in cancer studies.
• The system allows for the assessment of tumor microenvironment responses to therapeutic interventions.