Plant cell culture is an alternative supply source for plant derived pharmaceuticals which may have no other feasible method of commercial production. In comparison with microbial or mammalian cell culture, plant cell culture presents challenges including low and variable product yields and slow growth rates. One defining characteristic of plant cell suspension cultures is the tendency of cells to grow in aggregates. Plant cells remain connected after cell division, and as a result, aggregates ranging from two to several hundred cells (50 to 2000+ μm) are found in suspension, which can affect culture dynamics in several ways, including secondary metabolite accumulation and growth rate.

Taxus sp. cell culture for the production of the anti-cancer agent paclitaxel was used as a model system to investigate the effects of aggregate size on secondary metabolite accumulation. We developed a method to separate and subsequently screen different aggregate size fractions for paclitaxel and related taxanes using high performance liquid chromatography (HPLC). Aggregation dynamics in the culture system were phenomenologically described using a mathematical simulation correlated with experimental data. We used electrical zone sensing in conjunction with image analysis to collect aggregate size distribution data, and tracked the evolution of this distribution over the batch culture period. The model was formulated in a population balance equation framework, which could be directly compared to the distribution data collected. The comparison of the data and the model was used as meaningful criteria to evaluate the basic assumptions regarding aggregation phenomena that were used in structuring our model. This enhanced understanding of culture behavior can eventually be used as a tool to guide culture conditions to increase product accumulation.