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Challenges for the Cultivation of Plant Cells on the Example of Hypericum perforatum and Taxus chinensis

  • Mariam Gaid
  • Thomas Wucherpfennig
  • Stephan Scholl
  • Ludger Beerhues
  • Rainer Krull
Reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)

Abstract

Medicinal plants are sustainable bio-factories for valuable active pharmaceutical ingredients (API). They are commonly grown in the field and their extracts have a given combination of constituents. There is some variation due to climate fluctuations and plant diseases (microbial infections), genotypic changes, soil differences, etc. Additionally, fertile agricultural areas are increasingly limited. However, these variations are undesired because they are non-controllable and can affect the batch conformity of a drug significantly. This is a challenge for producers of phyto-pharmaceuticals, and the variations in the API composition are compensated by mixing extracts from various batches to achieve the required continuous quality of an authorized drug. These drawbacks of field cultivation are overcome by well-defined bioreactor-based cultivation. Biomass growth and API production take place under variable but controllable cultivation conditions, resulting in customized extracts. Variation of the cultivation conditions leads to qualitative and/or quantitative changes in the metabolome. During bioreactor cultivation, plant cells tend to stay connected after division, which leads to the formation of aggregates. The size of shear-sensitive plant cell aggregates influenced by hydrodynamic forces resulting from mechanical agitation was often recognized as an intangible parameter, which might be responsible for general variability in plant cell culture processes. To date, however, the bioreactor approach is not often industrially implemented. This chapter provides an overview of the challenges in the cultivation of plant cell systems, briefly illustrated by (i) research on Hypericum perforatum tissue cultures into up-to-date approaches for production of hyperforin and hypericin, possibly functional at a pre-commercial level in the future, and (ii) effects of hydrodynamic mechanical forces on Taxus chinensis submerged cultures for production of paclitaxel.

Abstract

Higher plants are an abundant source of bioactive and pharmaceutically important chemicals including drugs such as morphine, codeine, reserpine, and several alkaloids and steroids [1]. The world market for herbal medicines has reached US $ 60 billion, with annual growth rates of 5–15% [2]. Over 60% of anticancer drugs and 75% of drugs for infectious diseases currently used are made or extracted from natural sources [3]. The increasing demand for tailored phyto-pharmaceuticals with innovative active pharmaceutical ingredients (APIs) and activity profiles, produced by ecologically more sustainable bio-factories, and the significant reductions in biodiversity are driving efforts to find alternative ways of producing high-value plant-derived metabolites under well-defined cultivation conditions [4].

Keywords

Hypericum perforatum Hyperforin Hypericin Biodiversity In vitro cultures Taxus chinensis Plant cell aggregates Hydromechanical stress Cell viability 

Notes

Acknowledgments

The authors gratefully acknowledge financial support from the Lower Saxony Ministry for Science and Culture in the joint research project Novel synthesis and formulation methods for poorly soluble drugs and sensitive biopharmaceuticals (SynFoBiA) within the Center for Pharmaceutical Process Engineering (PVZ) at the Technische Universität Braunschweig, Germany.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Mariam Gaid
    • 2
    • 3
  • Thomas Wucherpfennig
    • 1
  • Stephan Scholl
    • 2
    • 3
  • Ludger Beerhues
    • 2
    • 3
  • Rainer Krull
    • 2
    • 3
  1. 1.Institute of Biochemical EngineeringTechnische Universität BraunschweigBraunschweigGermany
  2. 2.Institute of Pharmaceutical BiologyTechnische Universität BraunschweigBraunschweigGermany
  3. 3.Center of Pharmaceutical EngineeringTechnische Universität BraunschweigBraunschweigGermany

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