Expert view: Large‑scale stem cell expansion and differentiation

Cellular assays based on stem cell‑derived cells hold great promise in industrial drug research. To deliver robust results, reproducible processes for cell expansion and differentiation are needed; and the routine application of cell‑based assays requires the production of high cell numbers. Two‑dimensional systems such as T-fl asks and plates are widely used for the cultivation of stem cells but are limited in control and scalability. Stirred-tank bioreactors have emerged as promising alternative culture systems. We find more and more examples for the successful expansion of adherent cells in bioreactors, as cell aggregates or on microcarriers, including human induced pluripotent stem cells and tumour cell lines. It is in the bioreactor that the differentiation of stem cells into the desired cell type can take place. Stirred-tank bioreactor design has proven its value for efficient culture scaling, because it allows similar vessel geometries and capabilities at different scales. This facilitates a smooth transition to larger volumes and offers the option of process scale‑down for optimisation as well as troubleshooting.

A thorough understanding of how process parameters – such as pH, oxygen tension, and medium composition – influence cell growth, characteristics, and differentiation are needed. Bioprocess systems allow the close monitoring and control of these parameters. By statistical analysis of bioprocess data tracks, researchers gain comprehensive process understanding. Based on this they can develop control strategies, ensuring that set points are met throughout the culture and that conditions are comparable between batches.

Altogether, stirred‑tank bioreactors have great advantages to produce stem cell‑based products – by allowing expansion of adherent cells as cell aggregates, facilitating reproducible culture conditions, and being scalable.