Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Frank V. Ritacco; Yongqi Wu; Anurag Khetan

doi:10.1002/btpr.2706

journal article Oct 05, 2018

Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Frank V. Ritacco

Yongqi Wu Anurag Khetan

Biotechnology Progress Vol. 34 No. 6 pp. 1407-1426 · Wiley

View at Publisher Save 10.1002/btpr.2706

Abstract

The culture of Chinese Hamster Ovary (CHO) cells for modern industrial applications, such as expression of recombinant proteins, requires media that support growth and production. Such media must support high viable cell densities while also stimulating the synthesis and extracellular transport of biologic products. Early media development efforts in this area yielded basic formulations to sustain growth, viability, and cellular function, albeit comprising animal sourced components, and complex constituents used in batch culture mode. Subsequent improvements included the development of serum‐free and chemically defined (CD) media, the identification of critical nutrients, growth factors, and potentially inhibitory or toxic cellular metabolites, and the use of fed‐batch and perfusion culture techniques to optimize nutrient delivery while minimizing accumulation of unwanted waste products. This review is comprised of sections covering milestones in the evolution of mammalian cell culture media, nutrient composition and formulation requirements, optimization strategies, consistency and scalability of powder and liquid media preparation for industrial applications, and key recent advances driving progress in CHO cell culture medium design and development. © 2018 American Institute of Chemical Engineers
Biotechnol. Prog
., 34:1407–1426, 2018

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References

232

[1]

MorganJF MortonHJ ParkerRC.Nutrition of animal cells in tissue culture; initial studies on a synthetic medium. Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine (New York NY).1950;73(1):1–8. 10.3181/00379727-73-17557

[2]

Burgener A (2006)

[3]

10.1126/science.122.3168.501

[4]

10.1126/science.130.3373.432

[5]

10.1023/a:1007967602484

[6]

10.1016/0042-6822(59)90043-1

[7]

Hu W‐S (2012)

[8]

10.1073/pnas.53.2.288

[9]

10.1016/s0076-6879(79)58127-0

[10]

10.1073/pnas.79.4.1158

[11]

10.1001/jama.1967.03120080053007

[12]

10.1007/bf02620891

[13]

10.1016/b978-0-408-02732-8.50010-9

[14]

Murakami H "Serum‐free media used for cultivation of hybridomas" Adv Biotechnol Process (1989)

[15]

10.1007/s10616-004-6173-2

[16]

10.1002/bit.20746

[17]

10.1002/(sici)1097-0290(19971205)56:5<577::aid-bit11>3.0.co;2-9

[18]

10.1007/bf00762376

[19]

10.1002/bit.260431122

[20]

10.1002/bit.260431123

[21]

10.1002/bit.260460611

[22]

10.4161/mabs.2.5.12720

[23]

10.1002/bit.24602

[24]

10.1016/j.procbio.2011.03.014

[25]

10.1002/btpr.436

[26]

10.1016/j.ddtec.2008.12.003

[27]

10.1038/nbt1026

[28]

Schaub J "Advancing biopharmaceutical process development by system‐level data analysis and integration of omics data" Adv Biochem Eng Biotechnol (2012)

[29]

10.1002/bit.22549

[30]

10.1002/bit.23072

[31]

10.1002/bit.26259

[32]

10.1002/bit.26313

[33]

10.1007/s00253-015-6514-4

[34]

ConradDR. Sigma‐aldrich Media Expert.http://www.sigmaaldrich.com/life‐science/cell‐culture/learning‐center/media‐expert/sa‐media‐expert.html.

[35]

Riché E. (2010)

[36]

10.1002/biot.201100052

[37]

10.1002/(sici)1097-4652(199601)166:1<152::aid-jcp18>3.0.co;2-h

[38]

10.1002/bit.260390311

[39]

10.1016/j.procbio.2004.07.004

[40]

10.1002/bit.10013

[41]

10.1016/s0141-0229(00)00151-4

[42]

10.1021/bp9602360

[43]

10.1007/s12257-010-0409-0

[44]

10.1016/j.copbio.2013.04.016

[45]

10.1002/bit.20317

[46]

10.1021/bp990077v

[47]

10.1021/bp990124j

[48]

10.1002/bit.23075

[49]

10.1002/bit.20439

[50]

10.1016/j.jbiotec.2004.02.004

Showing 50 of 232 references

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Details

Published: Oct 05, 2018
Vol/Issue: 34(6)
Pages: 1407-1426
License: View

Authors

F

Frank V. Ritacco

Biologics Process Development Bristol‐Myers Squibb Pennington New Jersey United States

Y

Yongqi Wu

Biologics Process Development Bristol‐Myers Squibb Pennington New Jersey United States

A

Anurag Khetan

Biologics Process Development Bristol‐Myers Squibb Pennington New Jersey United States

Cite This Article

Frank V. Ritacco, Yongqi Wu, Anurag Khetan (2018). Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies. Biotechnology Progress, 34(6), 1407-1426. https://doi.org/10.1002/btpr.2706

Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

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