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 planar 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 microm), 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 mitochondrial 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.
Thouas
George A
GA
Monash University, Clayton Victoria, Australia. George.Thouas@eng.monash.edu.au
Thompson
Mark C
MC
Contreras
Karla G
KG
Liow
Keith Y S
KY
Tan
Kenny B T
KB
Hourigan
Keny
K
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation; D004058:Diffusion; D004867:Equipment Design; D005947:Glucose / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D012984:Software; D014407:Tumor Cells, Cultured / Q000166:cytology*
D019344:Lactic Acid; D005947:Glucose; D010100:Oxygen