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

The key advantage of a vertical bioreactor is the ability to achieve higher cell densities in culture, explained Michael Kallos, PhD, a professor at the University of Calgary, who told GEN that stirred tank reactors are not particularly suited to cell therapy manufacturing.

“In order to suspend the cells, and not have them settle and aggregate into large clumps, the stirred suspension bioreactor impeller needs to rotate and move the fluid. This also helps deliver oxygen throughout the volume.

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

Vertical bioreactors in combination with microcarriers

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

“The vertical-wheel bioreactor provides great mixing—which is good for oxygen delivery and suspending cells—without the high shear forces seen in 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, and in this way, we can 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 these types of bioreactors.”

And, although the vertical bioreactor and microcarrier combination described in the study was developed for the production of treatments for equine orthopedic injuries, it can be used for the production of human cell therapies, pointed out Kallos.

Bioreactor choices

In the future, cell therapy producers are going to need a range of bioreactor types, including both vertical and traditional stirred-tank systems, as production processes will continue to evolve, according to Kallos.

“There are going to be a number of technologies that will be used for cell therapies, and in particular the cell expansion phase. Autologous and allogeneic therapies have different needs—allogeneic will need protocols and technology for scale-up as generally there are fewer batches of large volumes, whereas autologous therapies will need a scale-out approach that supports many batches of small volumes,” he continued.

“Overall bioreactors offer many advantages over static traditional cell culture methods, including scalability, and process monitoring and control. These affect not only speed and cost, but more importantly impact cell quality, which is the real target.”

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