Skip to main content
SpringerLink
Log in

Chinese Hamster Cells in Biotechnological and Gerontological Research

  • REVIEW
  • Published:
Moscow University Biological Sciences Bulletin Aims and scope Submit manuscript

Abstract

One of the most frequently used model objects in gerontology is yeast, primarily Saccharomyces cerevisiae. Ample data indicating that the lesions in yeast undergoing chronological or stationary phase aging are similar to the age-related lesions in metazoan cells have been accumulated. However, yeast, similarly to any other study objects, also has drawbacks; in particular, although yeast cells are eukaryotes, they are evolutionarily far from mammals. This imposes limitations on the studies of non-conserved metabolic pathways in yeast. In some cases, mammalian cells (for example, Chinese hamster cells) are more suitable for chronological model experiments. They are widely used in industry for manufacturing monoclonal antibodies and recombinant proteins. A significant proportion of these products are produced after cessation of proliferation which initiates chronological aging of the culture. The accumulated data on the features of cell metabolism, as well as growth and duration of the functional activity of the cell culture, are extremely valuable for gerontologists. The exchange of information between these two branches—biotechnological and gerontological—will be beneficial to both of them.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Kaeberlein, M., Burtner, C.R., and Kennedy, B.K., Recent developments in yeast aging, PLoS Genet., 2007, vol. 3, no. 5, e84.

    PubMed  PubMed Central  Google Scholar 

  2. Longo, V.D., Shadel, G.S., Kaeberlein, M., and Kennedy, B., Replicative and chronological aging in Saccharomyces cerevisiae, Cell Metab., 2012, vol. 16, no. 1, pp. 18–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Aging research in yeast, in Subcellular Biochemistry, Breitenbach, M., Jazwinski, S.M., and Laun, P., Eds., Dordrecht–Heidelberg–London–New York: Springer, 2012.

    Google Scholar 

  4. MacLean, M., Harris, N., and Piper, P.W., Chronological lifespan of stationary phase yeast cells; a model for investigating the factors that might influence the ageing of postmitotic tissues in higher organisms, Yeast, 2001, vol. 18, no. 6, pp. 499–509.

    CAS  PubMed  Google Scholar 

  5. Fabrizio, P. and Longo, V.D., The chronological life span of Saccharomyces cerevisiae, Aging Cell, 2003, vol. 2, no. 2, pp. 73–81.

    CAS  PubMed  Google Scholar 

  6. Barnes, D.E. and Lindahl, T., Repair and genetic consequences of endogenous DNA base damage in mammalian cells, Ann. Rev. Genet., 2004, vol. 38, pp. 445–476.

    CAS  PubMed  Google Scholar 

  7. Faucher, F., Duclos, S., Bandaru, V., Wallace, S.S., and Doublié, S., Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinction, Structure, 2009, vol. 17, no. 5, pp. 703–712.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Herrera-Cruz, M.S. and Simmen, T., Of yeast, mice and men: MAMs come in two flavors, Biol. Direct, 2017, vol. 12, 3.

    PubMed  PubMed Central  Google Scholar 

  9. Morgunova, G.V. and Klebanov, A.A., Age-related AMP-activated protein kinase alterations: From cellular energetics to longevity, Cell Biochem. Funct., 2019, vol. 37, no. 3, pp. 169–176.

    CAS  PubMed  Google Scholar 

  10. Zimmermann, A., Hofer, S., Pendl, T., Kainz, K., Madeo, F., and Carmona-Gutierrez, D., Yeast as a tool to identify anti-aging compounds, FEMS Yeast Res., 2018, vol. 18, no. 6, foy020.

    CAS  PubMed Central  Google Scholar 

  11. Chartrain, M. and Chu, L., Development and production of commercial therapeutic monoclonal antibodies in mammalian cell expression systems: An overview of the current upstream technologies, Curr. Pharm. Biotechnol., 2008, vol. 9, no. 6, pp. 447–467.

    CAS  PubMed  Google Scholar 

  12. Jeong, D.W., Cho, I.T., Kim, T.S., Bae, G.W., Kim, I.H., and Kim, I.Y., Effects of lactate dehydrogenase suppression and glycerol-3-phosphate dehydrogenase overexpression on cellular metabolism, Mol. Cell. Biochem., 2006, vol. 284, no. 1–2, pp. 1–8.

    CAS  PubMed  Google Scholar 

  13. Lai, T., Yang, Y., and Ng, S.K., Advances in mammalian cell line development technologies for recombinant protein production, Pharmaceuticals, 2013, vol. 6, no. 5, pp. 579–603.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lewis, N.E., Liu, X., Li, Y., Nagarajan, H., Yerganian, G., O’Brien, E., Bordbar, A., Roth, A.M., Rosenbloom, J., Bian, C., and Xie, M., Genomic landscapes of Chinese hamster ovary cell lines as revealed by the cricetulus griseus draft genome, Nat. Biotechnol., 2013, vol. 31, no. 8, pp. 759–765.

    CAS  PubMed  Google Scholar 

  15. Fischer, S., Handrick, R., and Otte, K., The art of CHO cell engineering: A comprehensive retrospect and future perspectives, Biotechnol. Adv., 2015, vol. 33, no. 8, pp. 1878–1896.

    CAS  PubMed  Google Scholar 

  16. Brown, A.J. and James, D.C., Precision control of recombinant gene transcription for CHO cell synthetic biology, Biotechnol. Adv., 2016, vol. 34, no. 5, pp. 492–503.

    CAS  PubMed  Google Scholar 

  17. Golabgir, A., Gutierrez, J.M., Hefzi, H., Li, S., Palsson, B.O., Herwig, C., and Lewis, N.E., Quantitative feature extraction from the Chinese hamster ovary bioprocess bibliome using a novel meta-analysis workflow, Biotechnol. Adv., 2016, vol. 34, no. 5, pp. 21–633.

    Google Scholar 

  18. Hefzi, H., Ang, K.S., Hanscho, M., Bordbar, A., Ruckerbauer, D., Lakshmanan, M., Orellana, C.A., Baycin-Hizal, D., Huang, Y., Ley, D., and Martinez, V.S., A consensus genome-scale reconstruction of Chinese hamster ovary cell metabolism, Cell Syst., 2016, vol. 3, no. 5, pp. 434–443.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kim, J.Y., Kim, Y.G., and Lee, G.M., CHO cells in biotechnology for production of recombinant proteins: current state and further potential, Appl. Microbiol. Biotechnol., 2012, vol. 93, no. 3, pp. 917–930.

    CAS  PubMed  Google Scholar 

  20. Altamirano, C., Paredes, C., Cairó, J.J., and Gòdia, F., Improvement of CHO cell culture medium formulation: Simultaneous substitution of glucose and glutamine, Biotechnol. Prog., 2000, vol. 16, no. 1, pp. 69–75.

    CAS  PubMed  Google Scholar 

  21. Kim, S.H. and Lee, G.M., Functional expression of human pyruvate carboxylase for reduced lactic acid formation of Chinese hamster ovary cells (DG44), Appl. Microbiol. Biotechnol., 2007, vol. 76, no. 3, pp. 659–665.

    CAS  PubMed  Google Scholar 

  22. Li, J., Wong, C.L., Vijayasankaran, N., Hudson, T., and Amanullah, A., Feeding lactate for CHO cell culture processes: Impact on culture metabolism and performance, Biotechnol. Bioeng., 2012, vol. 109, no. 5, pp. 1173–1186.

    CAS  PubMed  Google Scholar 

  23. Toussaint, C., Henry, O., and Durocher, Y., Metabolic engineering of CHO cells to alter lactate metabolism during fed-batch cultures, J. Biotechnol., 2016, vol. 217, pp. 122–131.

    CAS  PubMed  Google Scholar 

  24. Brunner, M., Doppler, P., Klein, T., Herwig, C., and Fricke, J., Elevated pCO2 affects the lactate metabolic shift in CHO cell culture processes, Eng. Life Sci., 2018, vol. 18, no. 3, pp. 204–214.

    CAS  PubMed  Google Scholar 

  25. Zhou, M., Crawford, Y., Ng, D., Tung, J., Pynn, A.F., Meier, A., Yuk, I.H., Vijayasankaran, N., Leach, K., Joly, J., and Snedecor, B., Decreasing lactate level and increasing antibody production in Chinese hamster ovary cells (CHO) by reducing the expression of lactate dehydrogenase and pyruvate dehydrogenase kinases, J. Biotechnol., 2011, vol. 153, no. 1–2, pp. 27–34.

    CAS  PubMed  Google Scholar 

  26. Yip, S.S., Zhou, M., Joly, J., Snedecor, B., Shen, A., and Crawford, Y., Complete knockout of the lactate dehydrogenase A gene is lethal in pyruvate dehydrogenase kinase 1, 2, 3 down-regulated CHO cells, Mol. Biotechnol., 2014, vol. 56, no. 9, pp. 833–838.

    CAS  PubMed  Google Scholar 

  27. Noh, S.M., Park, J.H., Lim, M.S., Kim, J.W., and Lee, G.M., Reduction of ammonia and lactate through the coupling of glutamine synthetase selection and downregulation of lactate dehydrogenase-A in CHO cells, Appl. Microbiol. Biotechnol., 2017, vol. 101, no. 3, pp. 1035–1045.

    CAS  PubMed  Google Scholar 

  28. Oguchi, S., Saito, H., Tsukahara, M., and Tsumura, H., pH condition in temperature shift cultivation enhances cell longevity and specific hMab productivity in CHO culture, Cytotechnology, 2006, vol. 52, no. 3, pp. 199–207.

    CAS  PubMed  Google Scholar 

  29. Kim, Y.J., Baek, E., Lee, J.S., and Lee, G.M., Autophagy and its implication in Chinese hamster ovary cell culture, Biotechnol. Lett., 2013, vol. 35, no. 11, pp. 1753–1763.

    CAS  PubMed  Google Scholar 

  30. Fomina-Yadlin, D., Gosink, J.J., McCoy, R., Follstad, B., Morris, A., Russell, C.B., and McGrew, J.T., Cellular responses to individual amino-acid depletion in antibody-expressing and parental CHO cell lines, Biotechnol. Bioeng., 2014, vol. 111, no. 5, pp. 965–979.

    CAS  PubMed  Google Scholar 

  31. Yoon, S.K., Choi, S.L., Song, J.Y., and Lee, G.M., Effect of culture pH on erythropoietin production by Chinese hamster ovary cells grown in suspension at 32.5 and 37.0°C, Biotechnol. Bioeng., 2005, vol. 89, no. 3, pp. 345–356.

    CAS  PubMed  Google Scholar 

  32. Wilkens, C.A., Altamirano, C., and Gerdtzen, Z.P., Comparative metabolic analysis of lactate for CHO cells in glucose and galactose, Biotechnol. Bioprocess Eng., 2011, vol. 16, no. 4, pp. 714–724.

    CAS  Google Scholar 

  33. Tsao, Y.S., Cardoso, A.G., Condon, R.G., Voloch, M., Lio, P., Lagos, J.C., Kearns, B.G., and Liu, Z., Monitoring Chinese hamster ovary cell culture by the analysis of glucose and lactate metabolism, J. Biotechnol., 2005, vol. 118, no. 3, pp. 316–327.

    CAS  PubMed  Google Scholar 

  34. Lao, M.S. and Toth, D., Effects of ammonium and lactate on growth and metabolism of a recombinant Chinese hamster ovary cell culture, Biotechnol. Prog., 1997, vol. 13, no. 5, pp. 688–691.

    CAS  PubMed  Google Scholar 

  35. Kim, T.K., Ryu, J.S., Chung, J.Y., Kim, M.S., and Lee, G.M., Osmoprotective effect of glycine betaine on thrombopoietin production in hyperosmotic Chinese hamster ovary cell culture: Clonal variations, Biotechnol. Prog., 2000, vol. 16, no. 5, pp. 775–781.

    CAS  PubMed  Google Scholar 

  36. Kim, M.S., Kim, N.S., Sung, Y.H., and Lee, G.M., Biphasic culture strategy based on hyperosmotic pressure for improved humanized antibody production in Chinese hamster ovary cell culture, In Vitro Cell. Dev. Biol.-Anim., 2002, vol. 38, no. 6, pp. 314–319.

    CAS  PubMed  Google Scholar 

  37. Takagi, M., Hayashi, H., and Yoshida, T., The effect of osmolarity on metabolism and morphology in adhesion and suspension Chinese hamster ovary cells producing tissue plasminogen activator, Cytotechnology, 2000, vol. 32, no. 3, pp. 171–179.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang, X., Garcia, I.F., Baldi, L., Hacker, D.L., and Wurm, F.M., Hyperosmolarity enhances transient recombinant protein yield in Chinese hamster ovary cells, Biotechnol. Lett., 2010, vol. 32, no. 11, pp. 1587–1592.

    CAS  PubMed  Google Scholar 

  39. Warburg, O., On the origin of cancer cells, Science, 1956, vol. 123, no. 3191, pp. 309–314.

    CAS  PubMed  Google Scholar 

  40. Liberti, M.V. and Locasale, J.W., The Warburg effect: How does it benefit cancer cells?, Trends Biochem. Sci., 2016, vol. 41, no. 3, pp. 211–218.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Shestov, A.A., Liu, X., Ser, Z., Cluntun, A.A., Hung, Y.P., Huang, L., Kim, D., Le, A., Yellen, G., Albeck, J.G., and Locasale, J.W., Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step, eLife, 2014, vol. 3, e03342.

    PubMed Central  Google Scholar 

  42. DeBerardinis, R.J., Lum, J.J., Hatzivassiliou, G., and Thompson, C.B., The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation, Cell Metab., 2008, vol. 7, no. 1, pp. 11–20.

    CAS  PubMed  Google Scholar 

  43. Vander Heiden, M.G., Cantley, L.C., and Thompson, C.B., Understanding the Warburg effect: The metabolic requirements of cell proliferation, Science, 2009, vol. 324, no. 5930, pp. 1029–1033.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Brand, K., Aerobic glycolysis by proliferating cells: Protection against oxidative stress at the expense of energy yield, J. Bioenerg. Biomembr., 1997, vol. 29, no. 4, pp. 355–364.

    CAS  PubMed  Google Scholar 

  45. Zagari, F., Jordan, M., Stettler, M., Broly, H., and Wurm, F.M., Lactate metabolism shift in CHO cell culture: The role of mitochondrial oxidative activity, New Biotechnol., 2013, vol. 30, no. 2, pp. 238–245.

    CAS  Google Scholar 

  46. Hong, J.K., Nargund, S., Lakshmanan, M., Kyriakopoulos, S., Kim, D.Y., Ang, K.S., Leong, D., Yang, Y., and Lee, D.Y., Comparative phenotypic analysis of CHO clones and culture media for lactate shift, J. Biotechnol., 2018, vol. 283, pp. 97–104.

    CAS  PubMed  Google Scholar 

  47. Gray, J.V., Petsko, G.A., Johnston, G.C., Ringe, D., Singer, R.A., and Werner-Washburne, M., “Sleeping beauty”: quiescence in Saccharomyces cerevisiae, Microbiol. Mol. Biol. Rev., 2004, vol. 68, no. 2, pp. 187–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Wierman, M.B., Maqani, N., Strickler, E., Li, M., and Smith, J.S., Caloric restriction extends yeast chronological lifespan by optimizing the Snf1 (AMPK) signaling pathway, Mol. Cell. Biol., 2017, vol. 37, no. 13, e00562-16.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Buchsteiner, M., Quek, L.E., Gray, P., and Nielsen, L.K., Improving culture performance and antibody production in CHO cell culture processes by reducing the Warburg effect, Biotechnol. Bioeng., 2018, vol. 115, no. 9, pp. 2315–2327.

    CAS  PubMed  Google Scholar 

  50. Wilkens, C.A. and Gerdtzen, Z.P., Comparative metabolic analysis of CHO cell clones obtained through cell engineering, for IgG productivity, growth and cell longevity, PloS One, 2015, vol. 10, no. 3, e0119053.

    PubMed  PubMed Central  Google Scholar 

  51. Altamirano, C., Illanes, A., Becerra, S., Cairó, J.J., and Gòdia, F., Considerations on the lactate consumption by CHO cells in the presence of galactose, J. Biotechnol., 2006, vol. 125, no. 4, pp. 547–556.

    CAS  PubMed  Google Scholar 

  52. Gladden, L.B., Lactate metabolism: A new paradigm for the third millennium, J. Physiol., 2004, vol. 558, no. 1, pp. 5–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zilberter, Y., Zilberter, T., and Bregestovski, P., Neuronal activity in vitro and the in vivo reality: The role of energy homeostasis, Trends Pharmacol. Sci., 2010, vol. 31, no. 9, pp. 394–401.

    CAS  PubMed  Google Scholar 

  54. Wyss, M.T., Jolivet, R., Buck, A., Magistretti, P.J., and Weber, B., In vivo evidence for lactate as a neuronal energy source, J. Neurosci. Res., 2011, vol. 31, no. 20, pp. 7477–7485.

    CAS  Google Scholar 

  55. Pellerin, L., Bouzier-Sore, A.K., Aubert, A., Serres, S., Merle, M., Costalat, R., and Magistretti, P.J., Activity-dependent regulation of energy metabolism by astrocytes: An update, Glia, 2007, vol. 55, no. 12, pp. 1251–1262.

    PubMed  Google Scholar 

  56. Orozco, H., Matallana, E., and Aranda, A., Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions, Microb. Cell Fact., 2012, vol. 11, p. 104.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Aranda, A., Orozco, H., Picazo, C., and Matallana, E., Yeast life span and its impact on food fermentations, Fermentation, 2019, vol. 5, no. 2, p. 37.

    CAS  Google Scholar 

  58. Thomas, K.C., Hynes, S.H., and Ingledew, W.M., Influence of medium buffering capacity on inhibition of Saccharomyces cerevisiae growth by acetic and lactic acids, Appl. Environ. Microbiol., 2002, vol. 68, no. 4, pp. 1616–1623.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Morgunova, G.V., Klebanov, A.A., Marotta, F., and Khokhlov, A.N., Culture medium pH and stationary phase/chronological aging of different cells, Moscow Univ. Biol. Sci. Bull., 2017, vol. 72, no. 2, pp. 47–51.

    Google Scholar 

  60. Morgunova, G.V. and Klebanov, A.A., Impairment of the viability of transformed Chinese hamster cells in a nonsubcultured culture under the influence of exogenous oxidized guanoside is manifested only in the stationary phase of growth, Moscow Univ. Biol. Sci. Bull., 2018, vol. 73, no. 3, pp. 124–129.

    Google Scholar 

  61. Morgunova, G.V., Karmushakov, A.F., Klebanov, A.A., and Khokhlov, A.N., Studies into the effect of “mild” uncoupling with 2,4-dinitrophenol on the growth of Chinese hamster cell culture and its subsequent dying out in the stationary phase, Moscow Univ. Biol. Sci. Bull., 2019, vol. 74, no. 3, pp. 163–169.

    Google Scholar 

  62. Matés, J.M., Di Paola, F.J., Campos-Sandoval, J.A., Mazurek, S., and Márquez, J., Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer, Semin. Cell Dev. Biol., 2020, vol. 98, pp. 34–43.

    PubMed  Google Scholar 

  63. Khokhlov, A.N., Morgunova, G.V., and Klebanov, A.A., Demographic approaches to the study of aging on cell cultures, Moscow Univ. Biol. Sci. Bull., 2019, vol. 74, no. 4, pp. 262–267.

    Google Scholar 

  64. Yang, Y., Santos, A.L., Xu, L., Lotton, C., Taddei, F., and Lindner, A.B., Temporal scaling of aging as an adaptive strategy of Escherichia coli, Sci. Adv., 2019, vol. 5, eaaw2069.

Download references

Funding

This study was performed within the framework of the state assignment of Moscow State University, part 2 (basic research, no. AAAA-A16-116021660098-8).

Author information

Authors and Affiliations

  1. Evolutionary Cytogerontology Sector, School of Biology, Moscow State University, 119234, Moscow, Russia

    G. V. Morgunova

Authors
  1. G. V. Morgunova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. V. Morgunova.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

The author declares that she has no conflict of interests.

ADDITIONAL INFORMATION

The author’s ORCID: http://orcid.org/0000-0002-5259-0861

Additional information

Translated by M. Batrukova

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morgunova, G.V. Chinese Hamster Cells in Biotechnological and Gerontological Research. Moscow Univ. Biol.Sci. Bull. 75, 199–205 (2020). https://doi.org/10.3103/S0096392520040069

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0096392520040069

Keywords:

Search

Navigation