A microfluidic hanging drop-based spheroid co-culture platform for probing tumor angiogenesis

Area of Science:

• Biomedical Engineering
• Cell Biology
• Oncology

Background:

• Tumor angiogenesis is crucial for cancer growth and metastasis.
• In vitro models are needed to study angiogenesis and test anti-angiogenesis drugs.
• Existing methods for spheroid co-culture can be complex and time-consuming.

Purpose of the Study:

• To develop and validate a microfluidic hanging drop-based spheroid co-culture device (μ-CCD) for studying tumor angiogenesis.
• To enable the generation and co-culturing of embryoid bodies (EBs) and tumor spheroids (TSs).
• To assess the potential of the μ-CCD for anti-angiogenesis drug screening.

Main Methods:

• A microfluidic hanging drop-based co-culture device (μ-CCD) was designed and fabricated.
• Uniform-sized EBs (from ES-D3 cells) and TSs (from MDA-MB-231 or MCF-7 cells) were generated.
• EB-TS pairs were co-cultured in hanging droplets for up to 10 days to observe tumor-induced angiogenesis.
• Confocal imaging was used to quantify angiogenesis parameters.

Main Results:

• The μ-CCD successfully generated and co-cultured EBs and TSs.
• Significant increases in vessel percentage area and total vessel length were observed after 6 days of co-culturing, indicating tumor angiogenesis.
• The device demonstrated efficacy in testing an anti-angiogenesis drug on the co-cultured spheroids.

Conclusions:

• The microfluidic hanging drop co-culture device (μ-CCD) offers a simple, efficient, and stable platform for in vitro tumor angiogenesis studies.
• The μ-CCD facilitates the investigation of tumor-induced angiogenic sprouting and provides a valuable tool for anti-angiogenesis drug development.
• This technology has potential applications in various fields requiring spheroid co-culturing.