Implications of cellular heterogeneity on plant cell culture performance

Abstract

Plant cell culture is an attractive platform technology for production and supply of several important plant-derived medicinal products. A unique characteristic of these dedifferentiated cells is the ability to grow as multicellular aggregates in suspension culture. The presence of these nonuniform aggregates results in creation of distinct microenvironments, which induce variations in cellular metabolism that are dependent on spatial position. This heterogeneity can lead to unpredictable and suboptimal performance in large-scale bioreactors. This review focuses on the role of cellular aggregation on the observed heterogeneity associated with plant cell cultures. Techniques used to study aggregation at the culture level as well as flow cytometric-based techniques to investigate and characterize heterogeneity at the single cell level are discussed. We focus on the commercially relevant production of the anticancer agent paclitaxel in Taxus suspension culture. An understanding of culture heterogeneity can lead to the development of targeted strategies to optimize culture performance for supply of medicinal products.