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Applied Microbiology and Biotechnology

, Volume 98, Issue 10, pp 4311–4319 | Cite as

Mammalian cell culture synchronization under physiological conditions and population dynamic simulation

  • Uwe Jandt
  • Oscar Platas Barradas
  • Ralf Pörtner
  • An-Ping Zeng
Mini-Review

Abstract

The overall behavior of cell cultures is determined by the actions and regulations of all cells and their interaction in a mixed population. However, the dynamics caused by diversity and heterogeneity within cultures is often neglected in the study of cell culture processes. Usually, a bulk behavior is assumed, although heterogeneity prevails in most cases. It is, however, not valid to conclude from the bulk behavior to the single cell behavior. Instead, it is necessary to include the behavior and kinetics of subpopulations and their interactions into models in order to elucidate the dynamic effects occurring in typical cell cultures. Heterogeneity in cell cultures is largely caused by the progress of the cell cycle. Cell cycle-dependent dynamics resulting for example in variable transfection efficiencies or expression bistability have recently attracted attention. In order to elucidate cell cycle-dependent regulations in cell cultures, it is desirable to synchronize a culture with minimal perturbation, which is possible with different yield and quality using physical methods, but not possible for frequently used chemical, or whole-culture methods. Then, the culture is cultivated again under physiological conditions and subpopulation-resolved analysis and modeling approaches are applied. This should allow to account for the variable contributions of subpopulations to the whole behavior and also for obtaining hereto unaccessible dynamic information of cellular regulation. In this short review, we summarize techniques and key issues to be considered for successful synchronization, cultivation, and modeling in order to achieve the goal of better understanding cell culture at a population level.

Keywords

Synchronous growth Elutriation Dialysis bioreactor Population heterogeneity Cell cycle control Stochastic modeling Physical synchronization 

Notes

Acknowledgments

We would like to thank Stephen Cooper (University of Michigan Medical School, MI, USA), for intense and fruitful discussions about synchronization methods and especially the inability of whole-culture methods to produce correctly synchronized cell cultures. The joint research projects “SysLogics” and “SysCompart” are funded by the German Federal Ministry of Education and Research (BMBF), grant numbers FKZ 0315275A and FKZ 0315555A. The research project “TransExpress” is funded by Deutsche Forschungsgemeinschaft (DFG), grant number ZE 542/33.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Uwe Jandt
    • 1
  • Oscar Platas Barradas
    • 1
  • Ralf Pörtner
    • 1
  • An-Ping Zeng
    • 1
  1. 1.Hamburg University of Technology, Bioprocess and Biosystems EngineeringHamburgGermany

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