Iron Chelates – Trick or Treat?

By on November 1, 2011

Iron is an essential part of any serum-free media formulation. Cells need iron to maintain health and to continue to grow and divide. In nature, iron is delivered to cells through the iron binding protein transferrin. In serum containing cultures, iron is not an issue because serum contains transferrin. However, when formulating serum-free media formulations, iron has to be added to compensate for the absence of iron and transferrin in serum. Bovine transferrin and human plasma derived transferrin is widely used in many cell types, including stem cells. As cell lines in bioproduction, for example CHO, began to move toward animal-free media formulations, researchers searched for an animal-free iron replacement and found iron chelates. Iron chelates are animal-free, provide iron to cells, are very inexpensive, and easy to obtain.

The challenge to using iron chelates is that iron causes oxidation reactions that can damage cells. In addition, iron chelates can cause difficulties in downstream processing. Transferrin is nature’s solution because it is an iron binding protein that prevents the toxic effects of iron and maintains proper cellular iron homeostasis. Transferrin sequesters iron in a non-toxic form and delivers iron in a regulated way to maintain cell health. Transferrin has also been proven to increase performance, when compared to iron chelates, which was covered in a previous Cell Culture Dish Blog titled “Transferrin Improves the Performance of Serum-Free Media.” Another problem is that iron chelates do not work in several cell lines, including hybridoma, stem cells, and vero cells. Today, cell culture scientists have an alternative to human transferrin (plasma-derived) or bovine transferrin thanks to recombinant DNA technology. Recombinant Transferrin is available from companies like InVitria (Optiferrin), Sigma-Aldrich, Thermo-Fisher HyClone, SeouLin Bioscience and others that is animal-free, recombinant and provides iron to cells.

So are iron chelates a trick or treat? With new recombinant transferrin supplements, maybe the best answer is to go back to nature’s solution and utilize transferrin in cell culture. Using recombinant transferrin would provide the same benefits as iron chelates without the problems of toxicity in culture.

Please comment, we would really like to hear your thoughts on the use of iron chelates.

One Comment

  1. Andreas

    18 November, 2015 at 4:26 AM

    Thank you for your summary. Could you explain the problem of iron chelats in downstream processing or point me into a direction? I could not find any indication in the literature. Still, at the moment I am facing the problem to process a harvest of a chemically defined media, formulated with 12.5 mg/L Fe. The formulation is proprietary by the company, but I suspect it is either ferric citrate or a mixture of ferric sulphate and sodium citrate.

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