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Transcriptome Analysis of Single Cells
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Transcriptome analysis for the scale-down of a CHO cell fed-batch process.

Abdulaziz A Alsayyari1, Xiao Pan1, Ciska Dalm2

  • 1Bioprocess Engineering, Wageningen University & Research, PO Box 16, 6700 AA, Wageningen, The Netherlands.

Journal of Biotechnology
|May 26, 2018
PubMed
Summary
This summary is machine-generated.

Scaling down CHO cell fed-batch processes to the ambr 15 system accurately reflects performance. Both agitation methods in the ambr system yielded comparable results to the 10 L bioreactor.

Keywords:
AmbrCHO cell cultureFed-batchScale-downTranscriptome analysismAb production

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Area of Science:

  • Biotechnology
  • Cell culture engineering
  • Process development

Background:

  • Scaling down bioreactor processes is crucial for efficient development.
  • The ambr 15 system is a popular platform for small-scale cell culture.
  • Evaluating scale-down models requires comparing critical process parameters and outcomes.

Purpose of the Study:

  • To assess the scale-down fidelity of a Chinese hamster ovary (CHO) cell fed-batch process from a 10 L bioreactor to the ambr 15 system.
  • To compare the impact of two different agitation scale-down strategies on culture performance and gene expression.
  • To validate the ambr 15 system as a representative model for bench-scale bioreactor processes.

Main Methods:

  • Fed-batch culture of CHO cells in a 10 L bioreactor and scaled down to the ambr 15 system.
  • Application of two agitation scale-down principles: tip speed (1300 RPM) and power input per volume (800 RPM).
  • Analysis of transcriptome (gene expression) and metabolism (cell growth, product titer, glycosylation, metabolite profiles) for both scales and conditions.

Main Results:

  • Culture performance (cell growth, titer, glycosylation, metabolite rates) was comparable between the two agitation rates in the ambr system and the 10 L bioreactor.
  • Gene expression profiles converged after three days, indicating similar culture conditions.
  • Principal component analysis showed <6% variation in gene expression changes over time between scales, suggesting comparable cellular responses.

Conclusions:

  • The ambr 15 system provides representative culture performance for CHO cell fed-batch processes scaled down from a 10 L bioreactor.
  • Both agitation scale-down strategies evaluated in the ambr system yielded similar and comparable results to the larger scale.
  • The ambr 15 system is a reliable platform for process development and optimization of CHO cell cultures.