Improved oxygen diffusion and mechanical aggregation of tumor colonies in a novel stirred mini-bioreactor

The feasibility of a novel stirred bioreactor, the rotating aerial disk (RAD) design, was tested in this study. The novelty lies in its method of medium recirculation by convective airflow using a non-contact planer disc, a variation on a physically defined theoretical model. Computational predictions of improved oxygenation were confirmed by increases in measured dissolved oxygen, even at Reynolds numbers (100–200) where flow is mostly laminar. EL-4 mouse lymphoma cells grown for the first time as suspension cultures in the RAD bioreactor, were mechanically re-organization into dense, circular three-dimensional colonies (diameter 3–5 mm, thickness 5–800 μm), more rapidly than we have observed previously. Cell proliferation in the RAD vessels was similar to static cultures, although lactate production from glucose was significantly lower, suggesting a shift toward aerobic glycolysis. This possible reversal of the ‘Warburg effect’ was accompanied by a decrease in mitachondrial activity, perhaps reflecting a more quiescent cytoplasmic state. The RAD device may be useful as scalable, three-dimensional solid tumor model under more physiological conditions then static culture.