Vertical bioreactors could benefit the cell therapy industry

An equine cell therapy manufacturing process that uses vertical bioreactors could help the entire industry reduce production and ultimately product costs, according to the authors of a new study.

The main advantage of a vertical bioreactor is the ability to achieve higher cell densities in culture, explained Dr. Michael Kallos, professor at the University of Calgary GENE that stirred tank reactors are not particularly suitable for the production of cell therapies.

“In order to suspend the cells and prevent them from settling and clumping into large clumps, the impeller of the suspension bioreactor must rotate and move the liquid. This also contributes to the oxygenation of the entire volume.

“However, one of the biggest challenges when using stirred suspension bioreactors is the high shear forces and the variation of forces throughout the bioreactor volume. When you increase agitation to suspend larger particles and deliver more oxygen, you expose the cells to higher shear forces.”

Vertical bioreactors in combination with microcarriers

To address this problem, Kallos and co-authors used vertical bioreactors developed by PBS Biotech – in combination with microcarriers – to culture mesenchymal stromal cells (MSCs) from horse umbilical cord blood.

“The vertical wheel bioreactor ensures excellent mixing – which has a positive effect on oxygen supply and cell suspension – without the high shear forces that occur with stirred suspension bioreactors. Many cell types grow in bioreactors as small clusters or aggregates, but some cells need a surface to attach to in order to proliferate,” he said.

“In this case we use microcarriers, which are small particles that can be suspended in the bioreactor. Cells can attach to these particles and grow and divide. This allows us to have a large surface area for cell growth but also take advantage of the bioreactor environment and scalability. Without microcarriers, we would not be able to grow certain cell types in such bioreactors.”

And although the vertical bioreactor and microcarrier combination described in the study was designed to produce treatments for equine orthopedic injuries, it can be used to produce therapies using human cells, Kallos emphasized.

Selection of bioreactors

According to Kallos, cell therapy manufacturers will need a range of bioreactor types in the future, including both vertical and traditional stirred tank systems, as production processes continue to evolve.

“There will be a range of technologies used for cell therapies and particularly for the cell expansion phase. “Autologous and allogeneic therapies have different requirements – allogeneic require protocols and technology for scaling as there are generally fewer large volume batches, while autologous therapies require a scale-out approach that supports many small volume batches,” he continued .

“Overall, bioreactors offer many advantages over static traditional cell culture methods, including scalability and process monitoring and control. These not only affect speed and costs, but above all also cell quality, which is the real goal.”