A kinetic model for growth of callus derived from Eucommia ulmoides aiming at mass production of a factor enhancing collagen synthesis of animal cells

Callus induced from the leaves of Eucommia ulmoides, a medicinal woody plant, was cultivated to produce a factor capable of enhancing collagen synthesis in animal cells (FECS). However, the callus was too rigid to be divided into small pieces by a hydrodynamic force during the cultivation, which led to a slow callus growth characterized by enlargement of the callus size rather than increase in the callus number. Improved growth rate of the callus with smaller sizes and cavity formation in the central region of the callus with its enlargement, implied the occurrence of transfer limitation of nutrient(s) inside the callus. Distributions of the principal nutrients of sugar, nitrogen and dissolved oxygen concentrations across the cultivated callus were simulated by a kinetic model consisting of nutrients diffusion and bioreaction kinetics, suggesting that oxygen transfer in the callus was the limiting factor for the callus growth. A callus growth model considering the effect of the nutrients’ transfer and cell death kinetics in the callus which was caused by the oxygen depletion successfully described the callus enlargement process. Based on these results, a newly developed bioreactor with a fragmentation device enabled the callus to grow with enhanced growth rate by controlling the callus at small sizes during the cultivation.