Oxygen Consumption and Oxygen Diffusion Properties of Multicellular Spheroids from two Different Cell Lines

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Abstract
Multicellular spheroids are an in vitro tissue model in which the cells are supplied by diffusion of oxygen and substrates from the environmental growth medium (Sutherland et al., 1971). Since these substances are consumed when diffusing to the spheroid center, their concentration should decrease continuously towards the inner parts of the spheroids. Therefore, the location of the cells within the spheroid is an important determinant of the efficiency of the O2 and nutrient supply. The restriction of the O2 availability in the inner part of the spheroids may influence the metabolic and cell cycle state, and may even cause cell death, indicated by central necrosis in larger spheroids. Also, accumulation of metabolic waste products during spheroid growth may have an impact on cellular metabolism and viability. Multicellular tumor spheroids have been widely used in cancer research to study the interrelationship among metabolism, cell cycle state and response of tumor cells to various treatment modalities. Many of these investigations resulted in the conclusion that the supply of O2 plays a decisive role in controlling the responsiveness to treatment.