Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches

Abstract

In this study, several approaches were tested to optimise the production and recovery of the widely used anticancer drug Taxol® (paclitaxel) from culturable vascular stem cells (VSCs) of Taxus baccata, which is currently used as a successful cell line for paclitaxel production. An in situ product recovery (ISPR) technique was employed, which involved combining three commercial macro-porous resin beads (HP-20, XAD7HP and HP-2MG) with batch and semi-continuous cultivations of the T. baccata VSCs after adding methyl jasmonate (Me-JA) as an elicitor. The optimal resin combination resulted in 234 ± 23 mg of paclitaxel per kg of fresh-weight cells, indicating a 13-fold improved yield compared to the control (with no resins) in batch cultivation. This resin treatment was further studied to evaluate the resins’ removal capacity of reactive oxygen species (ROS), which can cause poor cell growth or reduce product synthesis. It was observed that the ISPR cultivations had fourfold less intracellular ROS concentration than that of the control; thus, a reduced ROS concentration established by the resin contributed to increased paclitaxel yield, contrary to previous studies. These paclitaxel yields are the highest reported to date using VSCs, and this scalable production method could be applied for a diverse range of similar compounds utilising plant cell culture. Graphical Abstract

Bioreactor Systems for Plant Cell Cultivation at the Institute of Plant Physiology of the Russian Academy of Sciences: 50 Years of Technology Evolution from Laboratory to Industrial Implications

“…Many bioreactor systems are hybrids of the batch and continuous cultivation regimes. This includes periodic substrate-fed cultures (the periodical addition of the nutrient medium or individual limiting components without the removal of cell biomass) [109][110][111][112], semi-continuous systems (the periodic addition of fresh medium, while removing part of the cell suspension) [113,114], two-stage systems [70,115], etc. Unlike continuous culture regimes (chemostats in particular), such hybrid systems imply periodic changes in suspension volume and velocity, periodic suspension dilution, as well as varying the specific growth rate, productivity, and other parameters [15,19,91].…”