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Cell Lines

Cell Lines

A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...

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Induction and Testing of Hypoxia in Cell Culture

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

Cell line development for continuous high cell density biomanufacturing: Exploiting hypoxia for improved

Nikolas Zeh¹, Patrick Schlossbauer¹, Nadja Raab¹

¹Institute of Applied Biotechnology, University of Applied Sciences Biberach, Biberach, Germany.

Metabolic Engineering Communications

|August 17, 2021

Summary

Engineered Chinese hamster ovary (CHO) cells harness hypoxia to boost biotherapeutic protein production. This novel system enhances cellular production capacities under oxygen-limited conditions, improving yields.

Keywords:

Biotechnology Cell line engineering Chinese hamster ovary Hypoxia Perfusion Recombinant protein expression

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Last Updated: Oct 23, 2025

Induction and Testing of Hypoxia in Cell Culture

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics

A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics

Published on: September 22, 2011

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Anaerobic Growth and Maintenance of Mammalian Cell Lines

Published on: July 21, 2018

Area of Science:

Biotechnology
Cell Biology
Bioprocess Engineering

Background:

Hypoxia negatively impacts biotherapeutic protein production in Chinese hamster ovary (CHO) cells, reducing productivity and growth.
Hypoxic conditions are common in high-density batch and perfusion fermentation processes.

Purpose of the Study:

To engineer novel CHO cell lines that leverage hypoxia to enhance biotherapeutic protein production.
To develop a new bioprocessing strategy utilizing oxygen shifts to improve production titers.

Main Methods:

Verified the hypoxia-responsive pathway in CHO cells by analyzing HIF1a, HIF1β, and VDL proteins.
Functionally analyzed hypoxia-response-elements (HREs) to create hypoxia-responsive expression vectors.
Developed engineered CHO cell lines and tested them in batch and perfusion cultures.

Main Results:

Engineered CHO cell lines demonstrated a significant 2.7-fold induction of protein expression (SEAP) under hypoxic conditions.
Successfully established a novel oxygen shift bioprocessing strategy using hypoxia induction.
Validated the effectiveness of the engineered cell system in improving production titers.

Conclusions:

Exploiting adverse hypoxic conditions can significantly optimize CHO cell productivity for biotherapeutic production.
The developed hypoxia-sensitive CHO cell system offers a promising avenue for overcoming oxygen limitation challenges in bioprocessing.
This approach provides a foundation for establishing improved cell systems for enhanced biomanufacturing.