Results demonstrated that for the recombinant CHO cell line studied, the addition of chemically defined feed to the basal
medium produced approximately a four-fold greater protein yield than any of the four different plant hydrolysates used. Also,
culture supplementation with different plant hydrolysates in combination with chemically defined feeds provided no advantage
in terms of increased protein production over the addition of a chemically defined feed on its own. Supplementing media with
plant hydrolysates may not always be the most efficient choice or may not offer the same increases in productivity available
from chemically defined feeds. Therefore, when culturing CHO cells for maximum protein production, it may be worthwhile to
compare different feed types. Bioreactor studies of a different CHO cell line also demonstrated that chemically defined feeds
in the culture provided slightly higher protein yields than the addition of a soy hydrolysate when the two feeds were added
at the same concentration. In addition, using a higher concentration of chemically defined feed A on day 0 followed by feed
B on day 6 yielded superior bioproductivity and proved the value of including multiple, and sometimes counter-intuitive, feeding
strategies when trying to maximize protein production.
In summary, using chemically defined feeds with CHO cell lines not only eliminates the variability associated with using plant
hydrolysates, but could also improve the productivity of biopharmaceutical protein manufacture and help move therapeutic proteins
into clinical trials more rapidly.
David (Xiaojian) Zhao is a technical area manager of media development, Richard Fike is a principal scientist, Cell Systems Division, Borka Naumovich is an associate scientist III, and Mark Stramaglia is a senior product manager, all at Invitrogen Corporation, Grand Island, NY, 716.774.6860, firstname.lastname@example.org
1. Mols J, Peeters-Joris C, Wattiez R, Agathos SN, Schneider YJ. Recombinant interferon-gamma secreted by Chinese hamster
ovary-320 cells cultivated in suspension in protein-free media is protected against extracellular proteolysis by the expression
of natural protease inhibitors and by the addition of plant protein hydrolysates to the culture medium. In Vitro Cell Dev
Biol Anim. 2005. Mar–Apr; 41(3–4):83–91.
2. Burteau CC, Verhoeye FR, Mols JF, Ballez JS, Agathos SN, Schneider YJ. Fortification of a protein-free cell culture medium
with plant peptones improves cultivation and productivity of an interferon-gamma-producing CHO cell line. In Vitro Cell Dev
Biol Anim. 2003 Jul–Aug;39(7):291–6.
3. Luo Y, Chen G. Combined approach of NMR and chemometrics for screening peptones used in the cell culture medium for the
production of a recombinant therapeutic protein. Biotechnol Bioeng. 2007 Aug 15;97(6):1654–9.
4. Stein A. Decreasing variability in your cell culture. Biotechniques. 2007 Aug;43(2):228–9.
5. Chun BH, Kim JH, Lee HJ, Chung N. Usability of size-excluded fractions of soy protein hydrolysates for growth and viability
of Chinese hamster ovary cells in protein-free suspension culture. Bioresour Technol. 2007 Mar;98(5):1000–5.