Transferrin Improves the Performance of Serum-Free Media

Iron is required by cells and iron is an essential part of any serum-free media formulation. Cells must maintain proper intracellular iron levels. Without iron, cells usually fail to divide after a few divisions. One problem that arises from iron in media is that iron possesses oxidant properties that damages cells [1]. Nature’s solution to this problem is transferrin, an iron binding protein that prevents the toxic effects of iron and also maintains proper cellular iron homeostasis [2, 3]. Thus, transferrin sequesters iron in a non-toxic form and delivers iron to cells in a regulated manner in order to maintain proper cell division.

Iron Compounds Compared
Iron CompoundGrowth Ratio
None100
Transferrin393
Ferric citrate311
Ammonium iron citrate249
Ferrous sulfate155
Iron (III) sulfate135
Ferrous ammonium sulfate99
Ammonium iron (III) sulfate102
Iron (III) chloride87
Iron (II) chloride105
Iron (III) diphosphate65

Many serum-free media formulations contain iron compounds as a substitute for transferrin. However, studies have shown that iron compounds and iron-chelators do not offer the same performance as transferrin. Eto et al. [4] found that transferrin increased cell growth 4-fold compared to medium without iron and significantly outperformed 9 iron compounds to stimulate the growth of hybridoma cells (Table I). Moreover, the performance of iron compounds is poor for many cell types in addition to hybridoma, including primary and stem cells.

The intake of iron by cells is not regulated when iron compounds are used in a media formulation. In one example, Kovar found that the use of ferric citrate resulted in intracellular iron levels 100-fold above normal physiological levels [5]. Thus, the use of transferrin in serum-free media offers performance and other advantages compared to iron compounds.

Recombinant transferrini seconomical,robust,and producedinananimalfre eproduction system.Thus, the robust performance of transferrin is now available to improve your cellculture.

  1. Garcia-Alfonso, C., J. Lopez-Barea, P. Sanz, G. Repetto, et al., Changes in antioxidative activities induced by Fe (II) and Fe (III) in cultured Vero cells. 1996. (8661525) Arch Environ Contam Toxicol. 30 (4): p. 431-6.
  2. Conrad, M.E., J.N. Umbreit, and E.G. Moore, Iron absorption and transport. 1999. Am J Med Sci. 318 (4): p. 213-29.
  3. Elliott, R.L., M.C. Elliott, F. Wang, and J.F. Head, Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture, and ultrastructural study. 1993. Ann N Y Acad Sci. 698: p. 159-66.
  4. Eto, N., K. Yamada, T. Shito, S. Shirahata, et al., Development of a protein-free medium with ferric citrate substituting transferrin for the cultivation of mouse-mouse hybridomas. 1991. Agric Biol Chem. 55 (3): p. 863-5.
  5. Kovar, J. and F. Franek, Growth-stimulating effect of transferrin on a hybridoma cell line: relation to transferrin iron-transporting function. 1989. (2721585) Exp Cell Res. 182 (2): p. 358-69.