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Cultivation of Mammalian Cells Using a Single-use Pneumatic Bioreactor System

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Published on: October 10, 2014

Improving performance of mammalian cells in fed-batch processes through "bioreactor evolution".

Holly L Prentice¹, Barbara N Ehrenfels, William P Sisk

¹Biogen Idec, Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA. hprentice@momentapharma.com

Biotechnology Progress

|February 22, 2007

Summary

Bioreactor evolution enhances mammalian cell lines for improved recombinant protein production. Selected cells show higher densities, viability, and product titers without compromising quality.

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Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation

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Area of Science:

Biotechnology
Cell line development
Bioprocessing

Background:

Recombinant protein production in mammalian cells is limited by cell density and viability in bioreactors.
Developing cell lines with enhanced performance is crucial for efficient biomanufacturing.

Purpose of the Study:

To improve bioreactor performance of Chinese Hamster Ovary (CHO) cell lines through a selective evolution process.
To enhance cell density, viability, and recombinant protein production in mammalian cell lines.

Main Methods:

Iterative selection of DG44 CHO host cells and a recombinant production cell line under harsh bioreactor conditions termed 'bioreactor evolution'.
Assessment of cell density, integral cell area, transfection efficiency, secretory potential, and growth factor independence.
Evaluation of product titer and quality in evolved recombinant cell lines.

Main Results:

Evolved host cells showed a 2-fold increase in peak cell density and a 72% increase in integral cell area.
Evolved cells maintained transfection efficiency and secretory potential, with a subpopulation becoming growth-factor-independent.
Evolved recombinant production cells exhibited a 38% increase in peak cell density, 30% increase in integral cell area, and 36% increase in product titer.

Conclusions:

Bioreactor evolution is an effective strategy to enhance mammalian cell line performance for recombinant protein production.
The evolved cell lines demonstrate improved growth characteristics and higher product titers, beneficial for fed-batch processes.
This simple selection approach improves host cell properties without impacting product quality.