Serum in Cell Culture – FBS Analog as an Alternative to FBS

Serum is the liquid part of the blood that is obtained as a supernatant when centrifuging a coagulated blood sample. Serum is therefore the blood plasma without the clotting factors and solid blood components. It contains proteins (albumins), polypeptides, metabolites, trace elements, electrolytes, nutrients and hormones.

Fetal calf serum is a major component of many nutrient media in cell culture. Due to its large number of proteins – including many growth factors – serum (or a serum substitute) is essential for in-vitro cultivation of cells. Serum substances also play an important role in inhibition or binding of proteases and undesirable substances.

In general, the younger the animal, the more growth factors and the fewer antibodies are found in its blood. And the more growth factors or fewer antibodies, the better the cell growth in culture. This is why FBS is commonly preferred over calf serum or serum of adult animals.

Fetal bovine serum (equivalent to fetal calf serum) is obtained from the blood of bovine fetuses. FBS contains a variety of growth factors and hardly any immunoglobulins (antibodies). The latter can be harmful to sensitive cells, as they sometimes lead to immune reactions on the cell surface and can thus be responsible for early cell damage in vitro. Sensitive cell types, such as embryonic stem cells can practically not be cultivated without FBS. However, despite its unique performance, there are numerous reasons why it is desirable to do without FBS:

1. Low availability: FBS is a by-product of slaughter and can only be obtained if a (not yet noticed) pregnant cow is slaughtered. However, this happens less and less often due to newer examination methods and animal protection laws. In addition, the amount of blood in a fetus is very small and it requires a number of 3-4 unborn animals to earn 1 L of serum.
2. Ethics: The blood for the serum production is taken from the fetus while still living – without anesthesia.
3. Price: Due to the limited availability, the price is subject to large fluctuations and is continuously increasing.

Due to these disadvantages of FBS, less sensitive cell types are often cultivated with NBCS (Newborn Calf Serum) instead of FBS. The NBSC is usually derived from the calves that result as a “waste product” of the New Zealand and Australian dairy industry. Unfortunately, NBCS is often of poor quality (high Hb content, high endotoxin content). The reason is that dairy cattle are commonly exposed to high doses of antibiotics and the slaughtering process is often not ideal in terms of hygiene conditions (especially in terms of avoiding contamination in the blood collection process) and stress.

FBS Analog is a bovine serum that is not produced from unborn calf blood but from milk calves grown for the high-end meat industry. These calves are kept under organic conditions (free of antibiotics) and slaughtered “gently”. The blood is taken from the anaesthetized animals using an optimized and contamination-free collection method. The serum is then gained through intensive cleaning and processing steps in order to show a final composition and performance that largely corresponds to that of the FBS. In short, it is a serum that is not derived from a fetus, but which best fulfils the positive characteristics of fetal calf serum.

Advantages:

1. High availability and therefore significantly lower price
2. No large price fluctuations as the quantity produced remains stable
3. Slaughter is carried out to high standards (taking into account animal welfare)

Who can use FBS Analog?
Cell culture users in the field of research / vaccine production / production of biopharma-ceuticals that

• use FBS so far, but are willing to try something new due to ethical concerns / price uncertainty (exception: embryonic stem cells, ESCs)
• are currently using NBCS, but are dissatisfied with the performance

For more information on the FBS Analog product, please refer to the product data sheet and specification.

There are many arguments supporting a completely serum-free cell culture, including

• Avoidance of qualitative and quantitative variations of the composition (problems in reproducibility).
• Chemically defined and controlled conditions in vitro.
• Avoidance of (unknown) microbial contamination.
• Possibility to selectively grow certain cell types and suppress undesired fibroblast growth.
• Independence from serum availability and price.
• Avoiding the suffering of bovine fetuses.
• Easier isolation of cell products (“Down-Stream Processing”).
• FBS does not provide a physiological environment for cultured cells. In the body, cells – with the exception of blood cells – never come into contact with plasma proteins.

In reality, however, one must always take into account the specific cell type and the intended use. Avoiding serum requires the addition of other substances, which can be both complex or chemically defined with recombinant proteins. Furthermore serum-free media are not necessarily cheaper than serum-containing media, as e.g. many growth factors are very expensive.

The most promising serum replacement development is lysates of human platelet concentrates.