Monitoring of Plant Cells and Tissues in Bioprocesses

  • Juliane SteingroewerEmail author
  • Christiane Haas
  • Katja Winkler
  • Carolin Schott
  • Jost Weber
  • Julia Seidel
  • Felix Krujatz
  • Sibylle Kümmritz
  • Anja Lode
  • Maria Lisa Socher
  • Michael Gelinsky
  • Thomas Bley
Reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Plant cell and tissue cultures represent a suitable alternative as production systems for valuable plant secondary metabolites. Unlike traditional extraction from agricultural grown plants, the active ingredient production in biotechnological processes with in vitro cultures takes place in closed bioreactors under controlled conditions. This allows a year-round production with constant quality and quantity. However, the development of biotechnological processes with plant in vitro cultures is often time-consuming and requires parallelized screening systems. Furthermore, the design, optimization, and control of economic processes presuppose knowledge about the physiological state of the biological system and the kinetic parameters of biomass and product formation. To gain access to these data, suitable process-monitoring methods are required which provide information about the physiology of the process, both on a macroscopic and on the single cell level. However, due to the morphology of plant cell and tissue cultures, many methods for bioprocess monitoring that are used for mammalian and microbial cultures are not applicable. This chapter covers methods that are appropriate for monitoring of biotechnological processes with plant cell and tissue cultures: The conductivity of the growth medium is a powerful parameter to estimate the growth of complex plant cell aggregates and tissue structures. The next section describes the application of the RAMOS – a small scale cultivation system – for heterotrophic and phototrophic plant cell and tissue cultures. Flow cytometry is a tool to obtain segregated data of bioprocesses. Further, we describe a novel approach of cell immobilization for physiological studies and the design of bioprocesses, the 3D Green Bioprinting.


Monitoring Conductivity Respiration activity Oxygen transfer Shake flask Evaporation Flow cytometry Ploidy Growth kinetic Green Bioprinting Immobilization 



2,4-Dichlorophenoxyacetic acid




Computer-aided design


Computer-aided manufacturing


Concentration of substrates/products in culture medium [g l−1]


Confocal laser scanning microscopy


Concentration of substrates/products in a hydrogel pore [g l−1]


Cell suspension culture


Carbon dioxide transfer [mmol l−1]


Carbon dioxide transfer rate [mmol l−1 h−1]


Evaporation-corrected carbon dioxide transfer rate [mmol l−1 h−1]


Maximum biomass-specific carbon dioxide transfer rate [mmol g−1 h−1]


Maximum carbon dioxide transfer rate [mmol l−1 h−1]


DNA content of the holoploid genome with chromosome number n


DNA content of the monoploid genome with chromosome number x


Concentration of biomass dry weight [g l−1]


Maximum concentration of biomass dry weight [g l−1]




Rate of evaporation [ml h−1]


Fluorescent ubiquitination-based cell-cycle indicator

G0/G1 phase

Cell cycle phase

G2/M phase

Cell cycle phase


High performance liquid chromatography


Hairy root culture(s)


Light emitting diode(s)


Linsmaier and Skoog medium


Murashige and Skoog medium


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Nuclear phase status:

n – means the chromosome number of the meiotically reduced genome irrespective of the ploidy

2n – means the chromosome number of the non-reduced genome


Number of data points


Organic light emitting diode(s)


Oxygen transfer [mmol l−1]


Oxygen transfer rate [mmol l−1 h−1]


Evaporation-corrected oxygen transfer rate [mmol l−1 h−1]


Maximum biomass-specific oxygen transfer rate [mmol g−1 h−1]


Maximum oxygen transfer rate [mmol l−1 h−1]


Oxygen uptake [mmol l−1]


Oxygen uptake rate [mmol l−1 h−1]


Overall pressure [bar]


Photosynthetic active radiation



\( {\mathrm{p}}_{{\mathrm{CO}}_2} \)

Carbon dioxide partial pressure [bar]


Photon flux density [μmol m−2 s−1]

\( {\mathrm{p}}_{{\mathrm{O}}_2} \)

Oxygen partial pressure [bar]


Universal gas constant (0.08314 bar l mol−1 K−1)


Respiration Activity MOnitoring System®


Respiration quotient


Concentration of substrate [g l−1]

S phase

Cell cycle phase


Scanning electron microscope


Time [d]


Initial liquid filling volume [ml]


Total flask volume [ml]


Number of chromosomes of the monoploid genome


Proportionality constant


Conductivity [mS cm−1]


Measured conductivity [mS cm−1]


Specific growth rate


Maximum specific growth rate



The authors thank Joachim Püschel and Dr. Beatrice Weber from the Institute of Botany, TU Dresden, for helpful discussions concerning the scheme in Fig. 10.


  1. 1.
    Zhong JJ (2001) Plant cells. Springer, BerlinCrossRefGoogle Scholar
  2. 2.
    Ludwig-Müller J, Gutzeit H (2014) Biologie von Naturstoffen: Synthese, biologische Funktionen und Bedeutung für die Gesundheit. Ulmer, StuttgartGoogle Scholar
  3. 3.
    Wink M (2003) Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 64:3–19PubMedCrossRefGoogle Scholar
  4. 4.
    Wink M (2010) Functions and biotechnology of plant secondary metabolites. Wiley-Blackwell, OxfordCrossRefGoogle Scholar
  5. 5.
    Wink M (1999) Biochemistry of plant secondary metabolism. Sheffield Academic Publishers, SheffieldGoogle Scholar
  6. 6.
    Schopfer P, Brennicke A, Mohr H (2006) Pflanzenphysiologie. Elsevier/Spektrum Akad. Verl, MünchenGoogle Scholar
  7. 7.
    Nessler CL (1994) Metabolic engineering of plant secondary products. Transgenic Res 3:109–115PubMedCrossRefGoogle Scholar
  8. 8.
    Steingroewer J, Bley T, Georgiev V, Ivanov I, Lenk F, Marchev A, Pavlov A (2013) Bioprocessing of differentiated plant in vitro systems. Eng Life Sci 13:26–38CrossRefGoogle Scholar
  9. 9.
    Winkler K (2015) Untersuchungen zur verfahrenstechnischen Verbesserung der Sekundärmetabolitproduktion mit pflanzlichen Zell- und Gewebekulturen. Dissertation, Technische Universität DresdenGoogle Scholar
  10. 10.
    Georgiev M, Ludwig-Müller J, Weber J, Stancheva N, Bley T (2010) Bioactive metabolite production and stress-related hormones in Devil’s claw cell suspension cultures grown in bioreactors. Appl Microbiol Biotechnol 89:1683–1691PubMedCrossRefGoogle Scholar
  11. 11.
    Ramachandra Rao S, Ravishankar GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnol Adv 20:101–153CrossRefGoogle Scholar
  12. 12.
    Eibl R, Eibl D (2008) Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev 7:593–598CrossRefGoogle Scholar
  13. 13.
    Zhong JJ (2001) Biochemical engineering of the production of plant-specific secondary metabolites by cell suspension cultures. Adv Biochem Eng Biotechnol 72:1–26PubMedGoogle Scholar
  14. 14.
    Fujita Y, Hara Y, Suga C, Morimoto T (1981) Production of shikonin derivatives by cell suspension cultures of Lithospermum erythrorhizon: II. A new medium for the production of shikonin derivatives. Plant Cell Rep 1:61–63PubMedCrossRefGoogle Scholar
  15. 15.
    Wickremesinhe ERM, Arteea RN (1993) Taxus callus cultures: initiation, growth optimization, characterization and taxol production. Plant Cell Tissue Organ Cult 35:181–193CrossRefGoogle Scholar
  16. 16.
    Weber J, Georgiev V, Haas C, Bley T, Pavlov A (2010) Ploidy levels in Beta vulgaris (red beet) plant organs and in vitro systems. Eng Life Sci 10:139–147Google Scholar
  17. 17.
    Georgiev MI, Pavlov AI, Bley T (2007) Hairy root type plant in vitro systems as sources of bioactive substances. Appl Microbiol Biotechnol 74:1175–1185CrossRefPubMedGoogle Scholar
  18. 18.
    Georgiev M, Heinrich M, Kerns G, Pavlov A, Bley T (2006) Production of iridoids and phenolics by transformed Harpagophytum procumbens root cultures. Eng Life Sci 6:593–596CrossRefGoogle Scholar
  19. 19.
    Matkowski A (2008) Plant in vitro culture for the production of antioxidants – a review. Biotechnol Adv 26:548–560PubMedCrossRefGoogle Scholar
  20. 20.
    Geipel K, Socher ML, Haas C, Bley T, Steingroewer J (2013) Growth kinetics of a Helianthus annuus and a Salvia fruticosa suspension cell line: shake flask cultivations with online monitoring system. Eng Life Sci 13:593–602CrossRefGoogle Scholar
  21. 21.
    Georgiev M, Georgiev V, Weber J, Bley T, Ilieva M, Pavlov A (2008) Agrobacterium rhizogenes-mediated genetic transformations: a powerful tool for the production of metabolites. In: Wolf TV, Koch JP (eds) Genetically modified plants. Nova, New YorkGoogle Scholar
  22. 22.
    Moore WJ, Hummel DO, Trafara G (1986) Physikalische Chemie, 4th edn. de Gruyter, BerlinCrossRefGoogle Scholar
  23. 23.
    Taya M, Yoyama A, Kondo O, Kobayashi T, Matsui C (1989) Growth characteristics of plant hairy roots and their cultures in bioreactors. J Chem Eng Jpn 22:84–89CrossRefGoogle Scholar
  24. 24.
    Mukundan U, Carvalho EB, Curtis WR (1998) Growth and pigment production by hairy root cultures of Beta vulgaris L. in a bubble column reactor. Biotechnol Lett 20:469CrossRefGoogle Scholar
  25. 25.
    Pavlov A, Bley T (2006) Betalains biosynthesis by Beta vulgaris L. hairy root culture in a temporary immersion cultivation system. Process Biochem 41:848–852CrossRefGoogle Scholar
  26. 26.
    Taya M, Hegglin M, Prenosil JE, Bourne JR (1989) On-line monitoring of cell growth in plant tissue cultures by conductometry. Enzyme Microb Technol 11:170–176CrossRefGoogle Scholar
  27. 27.
    Pavlov A, Georgiev V, Ilieva M (2005) Betalain biosynthesis by red beet (Beta vulgaris L.) hairy root culture. Process Biochem 4:1531–1533CrossRefGoogle Scholar
  28. 28.
    Murashige T, Skoog F (1962) A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol Plant 15:473–497CrossRefGoogle Scholar
  29. 29.
    Linsmaier EM, Skoog F (1995) Organic growth factor requirements of tobacco tissue cultures. Physiol Plant 1965 18:100–127Google Scholar
  30. 30.
    Haas C, Weber J, Ludwig-Muller J, Deponte S, Bley T, Georgiev M (2008) Flow cytometry and phytochemical analysis of a sunflower cell suspension culture in a 5-L bioreactor. Z Naturforsch C J Biosci 63:699–705CrossRefGoogle Scholar
  31. 31.
    Anderlei T, Büchs J (2001) Device for sterile online measurement of the oxygen transfer rate in shaking flasks. Biochem Eng J 7:157–162PubMedCrossRefGoogle Scholar
  32. 32.
    Anderlei T, Zang W, Papaspyrou M, Büchs J (2004) Online respiration activity measurement (OTR, CTR, RQ) in shake flasks. Biochem Eng J 17:187–194CrossRefGoogle Scholar
  33. 33.
    Büchs J (2002) Automatisches Meßsystem zur sterilen on-line Bestimmung der Sauerstofftransferrate (OTR) in Schüttelkolben. DE 44 15 444.5, 1994Google Scholar
  34. 34.
    Winkler K, Socher ML (2014) Shake flask technology. In: Flickinger MC (ed) Encyclopedia of industrial biotechnology: bioprocess, bioseparation, and cell technology. Wiley, New YorkGoogle Scholar
  35. 35.
    Wen ZY, Zhong JJ (1995) A simple and modified manometric method for measuring oxygen uptake rate of plant cells in flask cultures. Biotechnol Tech 9:521–526CrossRefGoogle Scholar
  36. 36.
    Büchs J (2001) Introduction to advantages and problems of shaken cultures. Biochem Eng J 7:91–98PubMedCrossRefGoogle Scholar
  37. 37.
    Amoabediny G, Büchs J (2010) Determination of CO(2) sensitivity of micro-organisms in shaken bioreactors. I. Novel method based on the resistance of sterile closure. Biotechnol Appl Biochem 57:157–166PubMedCrossRefGoogle Scholar
  38. 38.
    Bähr C, Leuchtle B, Lehmann C et al (2012) Dialysis shake flask for effective screening in fed-batch mode. Biochem Eng J 69:182–195CrossRefGoogle Scholar
  39. 39.
    Guez JS, Muller CH, Danze PM, Büchs J, Jacques P (2008) Respiration activity monitoring system (RAMOS), an efficient tool to study the influence of the oxygen transfer rate on the synthesis of lipopeptide by Bacillus subtilis ATCC6633. J Biotechnol 134:121–126PubMedCrossRefGoogle Scholar
  40. 40.
    Hansen S, Hariskos I, Luchterhand B, Büchs J (2012) Development of a modified Respiration Activity Monitoring System for accurate and highly resolved measurement of respiration activity in shake flask fermentations. J Biol Eng 6:1–12CrossRefGoogle Scholar
  41. 41.
    Kensy F, Engelbrecht C, Büchs J (2009) Scale-up from microtiter plate to laboratory fermenter: evaluation by online monitoring techniques of growth and protein expression in Escherichia coli and Hansenula polymorpha fermentations. Microb Cell Fact 8:1–15CrossRefGoogle Scholar
  42. 42.
    Meier K, Klöckner W, Bonhage B, Antonov E, Regestein L, Büchs J (2016) Correlation for the maximum oxygen transfer capacity in shake flasks for a wide range of operating conditions and for different culture media. Biochem Eng J 109:228–235CrossRefGoogle Scholar
  43. 43.
    Canzoneri M, Krüger R, Zang W, Biselli M (2006) Atmungsaktivität von Säugerzellen: Kontinuierliche Onlineermittlung im Schüttelkolben. BIOforum 3:45–47Google Scholar
  44. 44.
    Kowollik S, Schnitzler T, Biselli M et al (2010) Die Rolle des Respirationsquotienten in der Zellkulturfermentation. Chem Ing Tech 82:1505–1506CrossRefGoogle Scholar
  45. 45.
    Raval KN, Hellwig S, Prakash G, Ramos-Plasencia A, Srivast A, Büchs J (2003) Necessity of a two-stage process for the production of azadirachtin-related limonoids in suspension cultures of Azadirachta indica. J Biosci Bioeng 96:16–22PubMedCrossRefGoogle Scholar
  46. 46.
    Rechmann H, Friedrich A, Forouzan D, Barth S, Schnabl H, Biselli M, Boehm R (2007) Characterization of photosynthetically active duckweed (Wolffia australiana) in vitro culture by Respiration Activity Monitoring System (RAMOS). Biotechnol Lett 29:971–977PubMedCrossRefGoogle Scholar
  47. 47.
    Ullisch DA, Müller CA, Maibaum S et al (2012) Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled {GFP} and {HA} protein production by media optimization. J Biosci Bioeng 113:242–248PubMedCrossRefGoogle Scholar
  48. 48.
    Haas C, Hengelhaupt KC, Kümmritz S, Bley T, Pavlov A, Steingroewer J (2014) Salvia suspension cultures as production systems for oleanolic and ursolic acid. Acta Physiol Plant 36:2137–2147CrossRefGoogle Scholar
  49. 49.
    Schilling JV, Schillheim B, Mahr S, Reufer Y, Sanjoyo S, Büchs J (2015) Oxygen transfer rate identifies priming compounds in parsley cells. BMC Plant Biol 15:1–11CrossRefGoogle Scholar
  50. 50.
    Kümmritz S, Louis M, Haas C Oehmichen F, Gantz S, Delenk H, Steudler S, Bley T, Steingroewer J (2016) Fungal elicitors combined with a sucrose feed significantly enhance triterpene production of a Salvia fruticosa cell suspension. Appl Microbiol Biotechnol 100:7071–7082PubMedCrossRefGoogle Scholar
  51. 51.
    Geipel K, Bley T, Steingroewer J (2014) Charakterisierung pflanzlicher in vitro-Kulturen am Beispiel Sonnenblume. BIOspektrum 20:450–452CrossRefGoogle Scholar
  52. 52.
    Linden JC, Haigh JR, Mirjalili N, Phisaphalong M (2001) Gas concentration effects on secondary metabolite production by plant cell cultures. Adv Biochem Eng Biotechnol 72:27–62PubMedGoogle Scholar
  53. 53.
    Geipel K, Song X, Socher ML et al (2014) Induction of a photomixotrophic plant cell culture of Helianthus annuus and optimization of culture conditions for improved α-tocopherol production. Appl Microbiol Biotechnol 98:2029–2040PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Pavlov A, Werner S, Ilieva M, Bley T (2005) Characteristics of Helianthus annuus plant cell culture as a producer of immunologically active exopolysaccharides. Eng Life Sci 5:280–283CrossRefGoogle Scholar
  55. 55.
    Haas C (2007) Flow cytometric and phytochemical investigations with plant cell suspension cultures of sunflower (Helianthus annuus). Diploma thesis, Technische Universität DresdenGoogle Scholar
  56. 56.
    Krook J, Vreugdenhil D, van der Plas LHW (2000) Uptake and phosphorylation of glucose and fructose in Daucus carota cell suspensions are differently regulated. Plant Physiol Biochem 38:603–612CrossRefGoogle Scholar
  57. 57.
    Cohen Z (1999) Chemicals from microalgae. Taylor & Francis, LondonGoogle Scholar
  58. 58.
    Posten C (2009) Design principles of photo-bioreactors for cultivation of microalgae. Eng Life Sci 9:165–177CrossRefGoogle Scholar
  59. 59.
    Wang CY, Fu CC, Liu YC (2007) Effects of using light-emitting diodes on the cultivation of Spirulina platensis. Biochem Eng J 37:21–25CrossRefGoogle Scholar
  60. 60.
    Cerff M, Posten C (2012) Enhancing the growth of Physcomitrella patens by combination of monochromatic red and blue light – a kinetic study. Biotechnol J 7:527–536PubMedCrossRefGoogle Scholar
  61. 61.
    Socher ML, Löser C, Schott C, Bley T, Steingroewer J (2016) The challenge of scaling up photobioreactors: modeling and approaches in small scale. Eng Life Sci 16:598–609CrossRefGoogle Scholar
  62. 62.
    Socher ML, Lenk F, Geipel K Schott C, Püschel J, Haas C, Grasse C, Bley T, Steingroewer J (2014) Phototrophic growth of Arthrospira platensis in a respiration activity monitoring system for shake flasks (RAMOS®). Eng Life Sci 14:658–666CrossRefGoogle Scholar
  63. 63.
    Lehr F, Morweiser M, Sastre RR, Kruse O, Posten C (2012) Process development for hydrogen production with Chlamydomonas reinhardtii based on growth and product formation kinetics. J Biotechnol 162:89–96PubMedCrossRefGoogle Scholar
  64. 64.
    Krujatz F, Fehse K, Jahnel M et al (2016) MicrOLED-photobioreactor: design and characterization of a milliliter-scale Flat-Panel-Airlift-photobioreactor with optical process monitoring. Algal Res 18:225–234CrossRefGoogle Scholar
  65. 65.
    Sasabe H, Kido J (2013) Development of high performance OLEDs for general lighting. J Mater Chem C 1:1699–1707CrossRefGoogle Scholar
  66. 66.
    Galbraith DW, Harkins KR, Maddox JM, Ayres NM, Sharma DP, Firoozabady F (1983) Rapid flow cytometric analysis of the cell cycle in intact plant tissues. Science 220:1049–1051PubMedCrossRefGoogle Scholar
  67. 67.
    Haas C, Hegner R, Helbig K, Bartels K, Bley T, Weber J (2016) Two parametric cell cycle analyses of plant cell suspension cultures with fragile, isolated nuclei to investigate heterogeneity in growth of batch cultivations. Biotechnol Bioeng 113:1244–1250PubMedCrossRefGoogle Scholar
  68. 68.
    Greilhuber J, Doležel J, Lysák MA, Bennett MD (2005) The origin, evolution and proposed stabilization of the terms “genome size” and “C-value” to describe nuclear DNA contents. Ann Bot 95:255–260PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Palomino G, Dolezel J, Cid R, Brunner I, Méndez I, Rubluo A (1999) Nuclear genome stability of Mammillaria san-angelensis (Cactaceae) regenerants induced by auxins in long-term in vitro culture. Plant Sci 141:191–200CrossRefGoogle Scholar
  70. 70.
    Barow M, Meister A (2003) Endopolyploidy in seed plants is differently correlated to systematics, organ, life strategy and genome size. Plant Cell Environ 26:571–584CrossRefGoogle Scholar
  71. 71.
    Valente P, Tao W, Verbelen JP (1998) Auxins and cytokinins control DNA endoreduplication and deduplication in single cells of tobacco. Plant Sci 134:207–215CrossRefGoogle Scholar
  72. 72.
    Ochatt SJ (2008) Flow cytometry in plant breeding. Cytometry A 73A:581–598CrossRefGoogle Scholar
  73. 73.
    Kumar PS, Mathur VL (2004) Chromosomal instability in callus culture of Pisum sativum. Plant Cell Tissue Organ Cult 78:267–271CrossRefGoogle Scholar
  74. 74.
    Javadi S, Kermani MJ, Irian S, Majd A (2013) Indirect regeneration from in vitro grown leaves of three pear cultivars and determination of ploidy level in regenerated shoots by flow cytometry. Sci Hortic 164:455–460CrossRefGoogle Scholar
  75. 75.
    Jia Y, Zhang QX, Pan HT, Wang SQ, Liu QL, Sun LX (2014) Callus induction and haploid plant regeneration from baby primrose (Primula forbesii Franch.) anther culture. Sci Hortic 176:273–281CrossRefGoogle Scholar
  76. 76.
    Vrána J, Cápal P, Bednárová M, Doležel J (2014) Flow cytometry in plant research: a success story. In: Nick P, Zdenek O (eds) Applied plant cell biology. Springer, Berlin/HeidelbergGoogle Scholar
  77. 77.
    Vrána J, Šimková H, Kubaláková M, Čihaliková J, Doležel J (2012) Flow cytometric chromosome sorting in plants: the next generation. Methods 57:331–337PubMedCrossRefGoogle Scholar
  78. 78.
    Doležel J, Kubaláková M, Paux E, Bartoš J, Feuillet C (2007) Chromosome-based genomics in the cereals. Chromosome Res 15:51–66PubMedCrossRefGoogle Scholar
  79. 79.
    Castro S, Romeiras MM, Castro M, Duarte MC, Loureiro J (2013) Hidden diversity in wild Beta taxa from Portugal: insights from genome size and ploidy level estimations using flow cytometry. Plant Sci 207:72–78PubMedCrossRefGoogle Scholar
  80. 80.
    Hoshino Y, Eiraku N, Ohata Y, Komai F (2016) Dynamics of nuclear phase changes during pollen tube growth by using in vitro culture in Petunia. Sci Hortic 210:143–149CrossRefGoogle Scholar
  81. 81.
    Kamal KY, Hemmersbach R, Medina FJ, Herranz R (2015) Proper selection of controls in simulated microgravity research as illustrated with clinorotated plant cell suspension cultures. Life Sci Space Res 5:47–52CrossRefGoogle Scholar
  82. 82.
    Dhooghe E, Laere KV, Eeckhaut T, Leus L, Huyle JV (2010) Mitotic chromosome doubling of plant tissues in vitro. Plant Cell Tissue Organ Cult 104:359–373CrossRefGoogle Scholar
  83. 83.
    Jesus-Gonzalez LD, Weathers PJ (2003) Tetraploid Artemisia annua hairy roots produce more artemisinin than diploids. Plant Cell Rep 21:809–813PubMedGoogle Scholar
  84. 84.
    Pavlov A, Berkov S, Weber J, Bley T (2008) Hyoscyamine biosynthesis in Datura stramonium hairy root in vitro systems with different ploidy levels. Appl Biochem Biotechnol 157:210–225PubMedCrossRefGoogle Scholar
  85. 85.
    Škrlep K, Bergant M, Winter GMD et al (2008) Cryopreservation of cell suspension cultures of Taxus × media and Taxus floridana. Biol Plant 52:329–333CrossRefGoogle Scholar
  86. 86.
    Dolezel J, Greilhuber J, Suda J (2007) Flow cytometry with plant cells. Wiley-VCH Verlag GmbH & Co. KGaA, WeinheimCrossRefGoogle Scholar
  87. 87.
    Yanpaisan W, King NJC, Doran PM (1998) Analysis of cell cycle activity and population dynamics in heterogeneous plant cell suspensions using flow cytometry. Biotechnol Bioeng 58:515–528PubMedCrossRefGoogle Scholar
  88. 88.
    Jenzsch M, Gnoth S, Kleinschmidt M, Simutis R, Lübbert A (2006) Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile. Bioprocess Biosyst Eng 29:315–321PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Sonnleitner B (2000) Instrumentation of biotechnological processes. Adv Biochem Eng Biotechnol 66:1–64PubMedGoogle Scholar
  90. 90.
    Lidstrom ME, Konopka MC (2010) The role of physiological heterogeneity in microbial population behavior. Nat Chem Biol 6:705–712PubMedCrossRefGoogle Scholar
  91. 91.
    Hall RD, Yeoman MM (1987) Intercellular and intercultural heterogeneity in secondary metabolite accumulation in cultures of Catharanthus roseus following cell line selection. J Exp Bot 38:1391–1398CrossRefGoogle Scholar
  92. 92.
    Wilson SA, Cummings EM, Roberts SC (2014) Multi-scale engineering of plant cell cultures for promotion of specialized metabolism. Curr Opin Biotechnol 29:163–170PubMedCrossRefGoogle Scholar
  93. 93.
    Müller S, Harms H, Bley T (2010) Origin and analysis of microbial population heterogeneity in bioprocesses. Curr Opin Biotechnol 21:100–113PubMedCrossRefGoogle Scholar
  94. 94.
    Taticek RA, Moo-Young M, Legge RL (1991) The scale-up of plant cell culture: engineering considerations. Plant Cell Tissue Organ Cult 24:139–158CrossRefGoogle Scholar
  95. 95.
    Georgiev MI, Weber J, Maciuk A (2009) Bioprocessing of plant cell cultures for mass production of targeted compounds. Appl Microbiol Biotechnol 83:809–823PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Cebolla A, Vinardell JM, Kiss E, Oláh B, Roudier F, Kondorosi A, Kondorosi E (1999) The mitotic inhibitor ccs52 is required for endoreduplication and ploidy-dependent cell enlargement in plants. EMBO J 18:4476–4484PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Stancheva N, Weber J, Schulze J et al (2010) Phytochemical and flow cytometric analyses of Devil’s claw cell cultures. Plant Cell Tissue Organ Cult 105:79–84CrossRefGoogle Scholar
  98. 98.
    Yanpaisan W, King NJC, Doran PM (1999) Flow cytometry of plant cells with applications in large-scale bioprocessing. Biotechnol Adv 17:3–27PubMedCrossRefGoogle Scholar
  99. 99.
    Diermeier-Daucher S, Clarke ST, Hill D, Vollmann-Zwerenz A, Bradford JA, Brockhoff G (2009) Cell type specific applicability of 5-ethynyl-2′-deoxyuridine (EdU) for dynamic proliferation assessment in flow cytometry. Cytometry A 75:535–546PubMedCrossRefGoogle Scholar
  100. 100.
    Darzynkiewicz Z, Traganos F, Zhao H, Halicka HD, Li J (2011) Cytometry of DNA replication and RNA synthesis: historical perspective and recent advances based on “click chemistry”. Cytometry A 79:328–337PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Glab N, Labidi B, Qin LX, Trehin C, Bergounioux C, Meijer L (1994) Olomoucine, an inhibitor of the cdc2/cdk2 kinases activity, blocks plant cells at the G1 to S and G2 to M cell cycle transitions. FEBS Lett 353:207–211PubMedCrossRefGoogle Scholar
  102. 102.
    Tréhin C, Planchais S, Glab N, Perennes C, Tregear J, Bergounioux C (1998) Cell cycle regulation by plant growth regulators: involvement of auxin and cytokinin in the re-entry of Petunia protoplasts into the cell cycle. Planta 206:215–224PubMedCrossRefGoogle Scholar
  103. 103.
    Sakaue-Sawano A, Kurokawa H, Morimura T et al (2008) Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132:487–498PubMedCrossRefGoogle Scholar
  104. 104.
    Newman RH, Zhang J (2008) Fucci: street lights on the road to mitosis. Chem Biol 15:97–98PubMedCrossRefGoogle Scholar
  105. 105.
    Nishitani H, Lygerou Z, Nishimoto T (2004) Proteolysis of DNA replication licensing factor Cdt1 in S-phase is performed independently of geminin through its N-terminal region. J Biol Chem 279:30807–30816PubMedCrossRefGoogle Scholar
  106. 106.
    Zielke N, Edgar BA (2015) FUCCI sensors: powerful new tools for analysis of cell proliferation. Wiley Interdiscip Rev Dev Biol 4:469–487PubMedCrossRefGoogle Scholar
  107. 107.
    Yin K, Ueda M, Takagi H et al (2014) A dual-color marker system for in vivo visualization of cell cycle progression in Arabidopsis. Plant J 80:541–552PubMedCrossRefGoogle Scholar
  108. 108.
    Naill MC, Kolewe ME, Roberts SC (2012) Paclitaxel uptake and transport in Taxus cell suspension cultures. Biochem Eng J 63:50–56PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Doran PM (2006) Foreign protein degradation and instability in plants and plant tissue cultures. Trends Biotechnol 24:426–432PubMedCrossRefGoogle Scholar
  110. 110.
    Kirchhoff J, Raven N, Boes A et al (2012) Monoclonal tobacco cell lines with enhanced recombinant protein yields can be generated from heterogeneous cell suspension cultures by flow sorting. Plant Biotechnol J 10:936–944PubMedCrossRefGoogle Scholar
  111. 111.
    Moussaieff A, Rogachev I, Brodsky L et al (2013) High-resolution metabolic mapping of cell types in plant roots. Proc Natl Acad Sci 110:E1232–E1241PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Bargmann BOR, Birnbaum KD (2009) Positive fluorescent selection permits precise, rapid, and in-depth overexpression analysis in plant protoplasts. Plant Physiol 149:1231–1239PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Grasso MS, Lintilhac PM (2016) Microbead encapsulation of living plant protoplasts: a new tool for the handling of single plant cells. Appl Plant Sci 4. doi:10.3732/apps.1500140CrossRefGoogle Scholar
  114. 114.
    Kieran PM, Malone DM, MacLoughlin PF (2000) Effects of hydrodynamic and interfacial forces on plant cell suspension systems. In: Schügerl K, Kretzmer G (eds) Influence of stress on cell growth and product formation. Springer, Berlin/HeidelbergGoogle Scholar
  115. 115.
    Kieran PM, MacLoughlin PF, Malone DM (1997) Plant cell suspension cultures: some engineering considerations. J Biotechnol 59:39–52PubMedCrossRefGoogle Scholar
  116. 116.
    Rathore S, Desai PM, Liew CV, Chan LW, Heng PWS (2013) Microencapsulation of microbial cells. J Food Eng 116:369–381CrossRefGoogle Scholar
  117. 117.
    Singh B, Kaur A (2014) In vitro production of beneficial bioactive compounds from plants by cell immobilization. In: Kumar A (ed) Biotechnology. Plant biotechnology, vol 2. Studium Press LLC, New DelhiGoogle Scholar
  118. 118.
    Brodelius P (1985) The potential role of immobilization in plant cell biotechnology. Trends Biotechnol 3:280–285CrossRefGoogle Scholar
  119. 119.
    Huang TK, McDonald KA (2012) Bioreactor systems for in vitro production of foreign proteins using plant cell cultures. Biotechnol Adv 30:398–409PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Dörnenburg H, Knorr D (1995) Strategies for the improvement of secondary metabolite production in plant cell cultures. Enzyme Microb Technol 17:674–684CrossRefGoogle Scholar
  121. 121.
    Sabater-Jara AB, Tudela LR, López-Pérez AJ (2010) In vitro culture of Taxus sp.: strategies to increase cell growth and taxoid production. Phytochem Rev 9:343–356CrossRefGoogle Scholar
  122. 122.
    Malda J, Visser J, Melchels FP et al (2013) 25th anniversary article: engineering hydrogels for biofabrication. Adv Mater 25:5011–5028PubMedCrossRefGoogle Scholar
  123. 123.
    Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P (2012) A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33:6020–6041PubMedCrossRefGoogle Scholar
  124. 124.
    Lode A, Krujatz F, Brüggemeier S et al (2015) Green bioprinting: fabrication of photosynthetic algae-laden hydrogel scaffolds for biotechnological and medical applications. Eng Life Sci 15:177–183CrossRefGoogle Scholar
  125. 125.
    Derby B (2012) Printing and prototyping of tissues and scaffolds. Science 338:921–926PubMedCrossRefGoogle Scholar
  126. 126.
    Ozbolat IT (2015) Bioprinting scale-up tissue and organ constructs for transplantation. Trends Biotechnol 33:395–400PubMedCrossRefGoogle Scholar
  127. 127.
    Krujatz F, Lode A, Brüggemeier S et al (2015) Green bioprinting: viability and growth analysis of microalgae immobilized in 3D-plotted hydrogels versus suspension cultures. Eng Life Sci 15:678–688CrossRefGoogle Scholar
  128. 128.
    Schütz K, Placht AM, Paul B, Brüggemeier S, Gelinsky M, Lode A (2015) Three-dimensional plotting of a cell-laden alginate/methylcellulose blend: towards biofabrication of tissue engineering constructs with clinically relevant dimensions. J Tissue Eng Regen Med. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Juliane Steingroewer
    • 1
    Email author
  • Christiane Haas
    • 1
  • Katja Winkler
    • 1
  • Carolin Schott
    • 1
  • Jost Weber
    • 1
    • 3
  • Julia Seidel
    • 1
    • 4
  • Felix Krujatz
    • 1
  • Sibylle Kümmritz
    • 1
  • Anja Lode
    • 4
  • Maria Lisa Socher
    • 1
  • Michael Gelinsky
    • 4
  • Thomas Bley
    • 2
  1. 1.Institute of Natural Materials TechnologyTechnische Universität DresdenDresdenGermany
  2. 2.Bioprocess Engineering, Institute of Food Technology and Bioprocess EngineeringTU DresdenDresdenGermany
  3. 3.Evolva CopenhagenCopenhagenDenmark
  4. 4.Centre for Translational Bone, Joint and Soft Tissue Research, Faculty of Medicine Carl Gustav CarusTechnische Universität DresdenDresdenGermany

Personalised recommendations