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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Dissecting cell death pathways in fed-batch bioreactors.

David A Mentlak1, John Raven2, Tessa Moses3

  • 1Department of Biology, University of York, Heslington, York, UK.

Biotechnology Journal
|December 1, 2023
PubMed
Summary
This summary is machine-generated.

Cell death in Chinese hamster ovary (CHO) cells impacts biologic production. This study reveals non-apoptotic cell death pathways, like parthanatos and ferroptosis, contribute to viability loss in industrial CHO cell cultures.

Keywords:
CHO cellsParthanatosapoptosisferroptosisindustrial biotechnology

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Area of Science:

  • Biotechnology
  • Cell Biology
  • Biopharmaceutical Manufacturing

Background:

  • Chinese hamster ovary (CHO) cells are critical for producing biologics, including monoclonal antibodies.
  • Cell death in CHO cells significantly affects product yield and quality during biopharmaceutical manufacturing.
  • Apoptosis was previously considered the primary cell death mechanism in CHO cells within bioreactors.

Purpose of the Study:

  • To investigate the occurrence and mechanisms of cell death in an industrial antibody-producing CHO cell line under fed-batch culture conditions.
  • To determine if non-apoptotic cell death pathways contribute to viability loss in CHO cells during biopharmaceutical production.

Main Methods:

  • Analysis of cell viability in an industrial antibody-producing CHO cell line during fed-batch culture.
  • Assessment of apoptosis markers (e.g., caspase activation) under standard and stressed conditions.
  • Detection of markers for non-apoptotic cell death pathways, specifically parthanatos and ferroptosis.

Main Results:

  • A decrease in CHO cell viability was observed towards the end of standard fed-batch cultures without significant apoptosis markers.
  • Apoptosis was only induced under increased stress conditions, indicated by caspase activation.
  • Markers for parthanatos and ferroptosis were detected during standard fed-batch culture, suggesting their involvement in viability loss.

Conclusions:

  • Non-apoptotic cell death pathways, including parthanatos and ferroptosis, play a significant role in viability reduction in industrial CHO cell cultures.
  • Targeting these non-conventional cell death mechanisms offers a potential strategy to enhance cell viability and improve biologic production in CHO cells.