Product Survey: Cell culture media

No More Excuses
by Harald Zähringer, Labtimes 05/2015




Harvested whole blood with white blood cells, activated platelets and red blood cells. Platelet lysate extracted from expired human platelet units may replace FCS in cell culture. Photo: Jonathan Franks

The cell culture community is shaken by scandals of adulterated and mislabelled fetal calf serum (FCS) almost on a regular basis. At the same time, the number of serum-free media is steadily increasing. How many more FCS frauds will it take, to stop the “FCS business as usual” attitude of many researchers?

It’s time to switch from cell culture media, supplemented with fetal calf serum (FCS) to serum-free, chemically-defined media. That was the tenor of the product survey “Cell Culture Media” in Lab Times 4/2007 (page 53). Eight years later, however, many life science researchers still seem to be hanging on to their accustomed use of FCS − despite sky rocketing FCS prices, repeated frauds of adulterated fetal calf sera and a constantly growing list of chemically-defined media.

Prices for raw FCS derived from US cattle, which accounts for almost half of the worldwide FCS supply of approximately 600.000 litres (from which only 200.000 litres are assumed to be suitable for GMP manufacturing), exploded in the last years to 700 dollars per litre. FCS from Australia and New Zealand, producing another 20 % of the worldwide FCS supply, is even more expensive and sells well above 1.000 dollars. The major reason for the soaring prices is a multi-year drought in the USA, forcing ranchers in 2012 to dramatically cut down their livestock roving around the great western plains, leading to a severe FCS shortage.

FCS extracted from South American cattle, however, is a bargain compared to FCS from Oceania or the US: it goes over the counter for around 100 dollars. This ten-fold price span between the different origins is a perfect scenario for tricksters and dubious FCS brokers. It’s fairly easy to imagine their business strategy: simply buy cheap FCS from South American abattoirs, adulterate and expand it with low-grade sera or other obscure liquids and use false certificates from European slaughterhouses to sell the mixture as expensive, high quality FCS to clueless European customers.

FCS broker gang

That was basically the game plan of one FCS broker gang operating in the nineties from abattoirs in northern France, utilising the French FCS supplier, Biowest, as a distribution platform for the adulterated FCS. The illegal practices were uncovered when the Danish FCS producer, Sera Scandia, notified an ownership interest (i.e., purchasing considerable amounts of stocks or other assets to control a company) in Biowest in 1994 and acquired the company completely in 2004. Obviously, the Sera Scandia management had never heard of a due diligence examination, which is a standard investment business procedure, to audit a potential investment. It took them ten years to notice that something was wrong with their new daughter. Finally, the responsible manager was fired in 2004 and the case was put forward to the French police for further investigations.

But as you might guess, that was not the end of the FCS fraud story. According to a Fetal Bovine Serum hand-out, available at the Biowest website (www.biowest.net/download/fetal-bovine-serum-handout), it was just the beginning. The French investigators more recently unravelled another FCS broker gang in eastern France, which had mislabelled and adulterated 110.000 litres of Brazilian FCS between 2004 and 2014, and had shipped 50.000 litres as CE-marked FCS to Germany.

Clueless customers?

Meanwhile, the Biowest managers have taken the case to court in Baden-Baden, Germany, blaming competing FCS suppliers for having sold adulterated FCS and violating ethical standards, by not informing the clueless customers. The unappetising details of this recent FCS scandal were also reported in the German newspaper Die Süddeutsche and in the French gazette Le Courrier de l’Ouest.

But are FCS customers, i.e., life scientists, really that blank-faced, blissfully ignorant to what’s happening behind the FCS scenes? Come on! Researchers are no dummies, so they should definitely know what’s going on in the FCS business. And besides, which reasonable researcher really wants to depend on the weather conditions in the USA and the number of livestock in Texas? Let alone the ethical issues of FCS extraction and the not too unreal danger of FCS contamination with exotic viruses, bacteria, fungi or other obscure components.

So, the time has definitely come to throw away outdated habits and switch to serum-free, chemically-defined cell culture media. Even more so, since the often heard excuse that chemically-defined media supporting the growth of a specific cell line are hard to find, is becoming more obsolete − especially in stem cell research.

A recent review on the cultivation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) in xeno-free culture systems, lists 14 different, commercially available, serum-free media for hESC and hiPSC culture (Desai et al., Reprod. Biol. Endocrinol. 13, DOI 10.1186).

Some of them, like TeSR1 and E8, have been on the market for almost ten years. Others, such as StemFit, which has been developed in the lab of stem cell pioneer Joseph Itskovitz-Eldor at the Technion - Israel Institute of Technology in Haifa, are brand new. All specified media are basically composed of a simple, but highly defined, mixture of amino acids, vitamins, trace elements and growth factors.

The same holds true for the culture of standard cells, such as CHO-cells, fibroblasts or cancer cell lines. You may find commercial, serum-free media for maintaining the growth of almost every cell type. And even better: the number of completely chemically-defined media is also steadily increasing.

Completely defined, allround media

Cancer researchers may, for example, check out a new chemically-defined medium supporting the growth of different cancer cell lines. It has been elaborated by Rodney Nash and his co-workers at the Emory University School of Medicine, Atlanta, USA. Nash seems very convinced about the potential of his media formulation. He quit his postdoc position shortly after his invention in 2014 and founded the company Jeevan Biosciences to commercialise the medium under the brand name NeuroPure.

According to a recent paper from Jeevan Biosciences, Nash’s chemically-defined medium supports the growth of neuronal cells, cancer cells and fibroblasts (Ann. Transl. Med. (10):97. doi: 10.3978/j.issn). His start-up company is currently investigating, whether it is also suitable for other cell types such as iPSCs.

Human platelet lysate (hPL) extracted from expired human platelet units is another promising alternative to FCS (though it is not chemically-defined), which is especially useful for the expansion of mesenchymal stromal cells (MSCs). It is generated from platelet units by a simple freeze-thaw cycle process developed by Gerhard Gstraunthaler’s group at the University of Innsbruck, followed by centrifugation and filtration to remove cell fragments (Cytotherapy, 16: 170-80).

Platelet lysate delivers a complex mixture of growth factors and is applicable for different cell types, especially human MSCs, endothelial cells and fibroblasts. It is offered by specialised cell culture media companies and is also produced in small quantities by laboratories related to blood products or transfusion medicine, such as the Centre for Clinical Transfusion Medicine at the University of Tübingen, Germany.




First published in Labtimes 05/2015. We give no guarantee and assume no liability for article and PDF-download.


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