Two different serum-free media and osmolality effect upon human 293 cell growth and adenovirus production

Biotechnol Lett. 2005 Nov;27(22):1809-13. doi: 10.1007/s10529-005-3558-z.


Adenoviruses are promising vectors for gene therapy and vaccination protocols. Consequently, the market demands for adenovirus are increasing, driving the search for new methodologies for large-scale production of concentrated vectors with warranted purity and efficacy, in a cost-effective way. Nevertheless, the production of adenovirus is currently limited by the so-called 'cell density effect', i.e. a drop in cell specific productivity concomitant with increased cell concentration at infection. Of two different serum-free culture media (CD293 and EX-Cell), evaluated for their effect on human 293 cells growth and adenovirus production at cell densities higher than 1x10(6) cells/ml, EX-Cell proved the better medium for cell growth. Although adenovirus production was equivalent in both media when the infection was performed at 1x10(6) cells/ml, at 3x10(6) cells/ml CD293 was the better. This result related to the high ammonia content in EX-Cell medium at the highest cell concentration at infection. Besides this, the large-scale production of these vectors at high cell densities often requires re-feed strategies, which increase medium osmolality. While a negative effect on cell growth was observed with increasing osmolalities, adenovirus productivity was only affected for osmolalities higher than 430 mOsm.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / growth & development*
  • Adenoviridae / isolation & purification*
  • Cell Culture Techniques / methods*
  • Cell Line
  • Cell Proliferation
  • Culture Media, Serum-Free
  • Kidney / embryology
  • Kidney / growth & development*
  • Kidney / virology*
  • Osmolar Concentration
  • Virus Cultivation / methods*


  • Culture Media, Serum-Free