Producing Stem-Cell Aggregates Using Bioprinting

Researchers from Heriot-Watt University in Edinbugh and Roslin Cellab in the UK describe a method for producing uniformly sized spheroids composed of human embryonic stem cells in the Feb. 4, 2013 issue of the journal Biofabrication. According to the authors, creation of uniformly sized spheres is essential to controlling differentiation of stem cells. Previous attempts to use 3-dimensional bioprinting to automate the process and thereby produce structures of more consistent size have been unsuccessful because of poor cell viability. Human stem cells, they say, are particularly fragile and often do not survive the printing process.

In the current study, they use a valve-based cell printer to deposit two layers of liquid, or “bio-ink.” One layer consisted of cell-culture medium containing human embryonic stem cells, and a second layer contained medium alone. The volume of each ink droplet could be controlled independently, and varying the volume allowed control of the size of the resulting droplet and the number of cells contained within. A large-bore nozzle was used to reduce shear stress on the cells. After deposition into a microwell, the droplets were inverted, and the stem cells adhered to each other to form uniformly sized, spherical aggregates with cell viability of greater than 89% after 72 hours.

The authors suggest that the combination of speed, reproducibility, and the high degree of cell viability afforded by the process make it a promising system for production of stem-cell derived tissue for in vitro drug development, toxicity testing, or as clinical trial material.