A fully-automated bioreactor to culture human-induced pluripotent stem cells (hiPSCs) long-term has been developed by researchers at the Fraunhofer Translational Center for Regenerative Therapies. This bioreactor represents a key step forward in terms of producing commercial quantities of hiPSC for therapeutics.
“The bioreactors can be scaled in any size, according to customer requirements,” Thomas Schwarz, head of lab automation and bioreactor technologies, tells GEN. Currently, “Our bioreactors have a volume of 100 ml,” which is adequate for the cell quantities his lab uses.
The Fraunhofer dynamic incubator and suspension bioreactor has cultured cells and maintained their pluripotency for up to three months. Key benefits include full automation and modularity of the bioreactor, and a novel impeller design that ensure homogeneity within the cell culture.
Scientists estimate the number of cells needed for such therapeutics at approximately 109 cells per dose, with multiple doses required. Consequently, the demand for iPSCs is expected to grow at a compound annual growth rate of 9.4 percent from now until 2030, according to Grand View Research.
Ensuring optimum Conditions
Fraunhofer’s modular incubator and bioreactor system features a fluid loop that transports all the solutions for the process in sterile conditions, thus reducing human involvement and the risk of contamination. Other elements optimize the cell culture, maintaining a constant 37°C temperature and an atmosphere saturated with five percent carbon dioxide. Artificial intelligence counts cells and analyzes their geometry.
Schwarz and his team redesigned the impeller to improve homogenous conditions for the suspended cells. “The impeller is designed with the help of multiphysics simulation software,” he tells GEN. “So we can control the shear forces acting on the cells.”
The redesigned impeller also manages aeration, heat and mass transfer inside the bioreactor to enhance cell propagation and reproducibility. Internal sensors monitor bioreactor conditions in real time, thus making it possible for them to be aligned the optimal conditions for the impeller. In this way, the bioreactor ensures homogenous conditions regardless of cell quantity.
Because the bioreactor is modular, it can be expanded to include additional functions. Schwarz says these can include:
- Automatic media exchange and adding
- Automatic cells passaging
- Automatic microscope research
- Controlled cultivation conditions
- Different bioreactor sizes
- Automatic media stockage
Importantly, each of the modules—including various types of bioreactors—can be adjusted separately. This flexibility affects not only general functions, but enables the system to be adjusted to support different types of cultures and, therefore, a variety of cell differentiations.
Schwarz says the next goals for the bioreactor’s development are to “reduce the general size of the device” and to make it applicable for organoid and spheroid systems.
