Summary:
UCLA researchers in the Department of Mechanical and Aerospace Engineering have developed a simple, innovative method for growing 3D cell cultures with improved organoid differentiation and reduced hypoxia-induced cell death.
TITLE: Multiwell Plate-Based Flow Culture for Improving the Quality of 3D Tissues
Background:
3D tissue culture, with a market currently valued at over $1.5 billion with an estimated growth of 15% over the next 10 years, is an important technology enabling research on cancer, stem cells, and drug discovery. Static culture methods rely on diffusion to supply the growing tissue with necessary nutrients and oxygen, leading to stunted growth and hypoxic necrosis. Current state-of-the-art flow methods are not compatible with individual culture and require large amounts of media. In addition to relying on complex instrumentation, they do not allow for easy replication, and fail to generate uniform shear stress. Without uniform stress applied, cultured tissues fail to develop structural details necessary to better replicate in vivo experiments. There is a clear need for an ability to grow organoids more accurate to in vivo conditions.
Innovation:
UCLA researchers led by Professor Lin and his team have developed a novel, simple-to-use 3D tissue culture system which improves outcomes of stem cells developing into target tissues and reduces injury to cells due to lack of oxygen. This method is compatible with standard incubators using accessible 3D printed parts. The device is compatible with standard 96-well plates and is operable inside incubators while requiring less than a third of media compared to a spinner flask or bioreactor. Preliminary results demonstrated its efficacy, with spheroids seeing a 30% reduction in necrotic core size, more developed vasculature, and increased numbers of live cells on edges of samples.
Potential Applications:
• Metabolic assays
• Drug discovery
• Patient-derived explants for personalized medicine
• Stem cell research
• High-throughput organoid growth
Advantages:
• Compatible with standard incubators
• Cost-effective 3D printed parts
• Increased oxygenation of culture environment
• 30% reduction in necrosis of tissue
• Increased growth rate of tissue
Development to Date:
The researchers have successfully demonstrated efficacy of the flow culture and demonstrated utility in the growth of 3D organoids which are larger, have more developed vasculature, and display less hypoxia-indued apoptosis than static 3D tissue culture.
Related Papers:
Payne, Ho, Hashimoto, Imboden, Lee, Rupert, Cai, Goldstein, & Lin, bioRxiv 2022.06.28.498007. https://doi.org/10.1101/2022.06.28.498007.
Reference:
UCLA Case No. 2022-067
Lead Inventor:
Yen-Chih (Neil) Lin