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Related Concept Videos

Cell Culture01:21

Cell Culture

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Most vertebrate cells grow in vitro attached to a substrate as a monolayer, called adherent cultures. The flasks and plates used to grow cells are chemically treated to facilitate cell attachment. However, a few cell types, such as hematopoietic cells, can grow in a suspension. In contrast to adherent cultures, suspension cultures can grow in non-treated cultureware using magnetic stirrers or spinner flasks to agitate the culture media
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Engineering mammalian cell growth dynamics for biomanufacturing.

Mauro Torres1, Dewi Mcconnaughie1, Samia Akhtar1

  • 1Manchester Institute of Biotechnology, Faculty of Science and Engineering, University of Manchester, Manchester, UK; Department of Chemical Engineering, Biochemical and Bioprocess Engineering Group, University of Manchester, Manchester, UK.

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Summary

This study engineered mammalian cells for precise growth control in biopharmaceutical manufacturing. Synthetic biology tools were used to create tunable "gas and brake" systems for regulating cell growth dynamics.

Keywords:
BiopharmaceuticalsCRISPR-Cas9Cell engineeringGenetic circuitsProliferation control

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Area of Science:

  • Synthetic Biology
  • Cell Engineering
  • Biopharmaceutical Manufacturing

Background:

  • Mammalian cell growth dynamics present challenges in biopharmaceutical production.
  • Controlling cell proliferation and lifespan is crucial for optimizing manufacturing processes.

Purpose of the Study:

  • To develop a multi-level cell engineering strategy for tunable regulation of mammalian cell growth phases.
  • To create a dual controllable system for precise orchestration of cell growth dynamics.

Main Methods:

  • CRISPR/Cas9 gene editing to knockout pro-apoptotic proteins (Bax and Bak) for extended lifespan.
  • Abscisic acid inducible system regulating cMYC for growth acceleration.
  • Tetracycline inducible genetic circuit regulating BLIMP1 for growth arrest.

Main Results:

  • Engineered cells showed attenuated apoptosis, improved viability, and extended culture lifespan.
  • Achieved rapid cell density increase and cell cycle control via the growth acceleration system.
  • Demonstrated cell growth cessation and cell cycle arrest using the stationary phase induction system.
  • Developed a dual system for dynamic and precise control over mammalian cell growth phases.

Conclusions:

  • The developed strategy offers a sophisticated framework for manipulating mammalian cell growth.
  • This approach enhances biopharmaceutical manufacturing by enabling precise control over cell behavior.
  • The synthetic biology tools and combinatorial engineering provide a novel paradigm for biomedical applications.