By Alice de Bernardy
In biomedical research, cell cultures are widely used to model in vitro the response of different cell lines to different treatments or manipulations, in order to further understand how humans work.
To grow cells in a dish, researchers need to mimic the right environment for the cells to proliferate and keep their properties as much as possible to their in vivo equivalent. This is done by using different growth culture media supporting cell proliferation. One of the main components used widely to supplement cell culture media is Fetal Bovine serum, (FBS or FCS). The use of this component however can lead to debate due to ethics concerns.1
FCS is a serum extracted from unborn calves at the end of development[BK1] . The technique consists of draining the foetus’s blood, via a direct puncture of the heart, leading to the death of the calf. The use of FCS is problematic for animal welfare reasons and is less ideal for accurate research and reproducibility purposes. This is because FCS is not obtained from a synthetic source; batches vary among each other compromising the reproducibility of experiments. 2,3 For example, FBS has been found to induce differentiation when culturing human bone marrow mesenchymal stem cells resulting in cell culture instability and compromising any further assay.2 Also, FCS contains about 8% of proteins, but in vivo, cell lines each have a different interaction with their environment and the conditions for cell stability and division all varies under physiological conditions.2
Finally, FCS carries safety issues, as some batches have been found to be contaminated by viruses, compromising cell culture, which raises even more biosafety concerns when, for example, cells cultured are for a transplant or replacement therapy.2
Overall, batches of FCS need to be carefully screened before use. But what would it mean to stop using FCS as a supplement?
An alternative to FCS can be obtained from human platelets lysates. This concentrate contains hPR, a growth factor enabling cell culture expansion as well as low levels of protein. These lysates are usually used for transfusion to patients with platelets deficiency. However, due to medical safety the platelets expire after 5 days, but, after this period of time, hPR could be used for cell culture. Its worth noting this is not a solution to improve accuracy between batches and supply consistency.2
More and more serum-free solutions have been developed for cell culture. It has first been done to mimic the cerebra-spinal fluid (CSF) in order to grow primary neurons. The serum-free solution means that a very close idea of what’s in the growth medium is known, enabling precise control of cell growth, unlike with the use of FCS.3
One of the major emerging fields to rely on other supplements than FCS is in the domain of stem cells research. For example, manipulating pluripotent stem cells or iPSC requires a precise control of the cell’s gene expression pattern to stably maintain and control the differentiation of the cells. The use of serum is not appropriate and finely tuned growth medias are used. For example, a Xeno-Free Serum substitute (XFS2, Celprogen) enables culture of a wide array of human cells, from stem cells and progenitors to cancer cells.2This serum being made from entirely synthetic component is a good example of the future of cell culture.
In the end, if the research world wants to exit from the use of FCS, it would ideally require the development of serum-free growth medium tailored to each cell line. This means a lot of research and testing but could in the end enable much precise control of cells in culture and exit from the dependance on FCS and the ethics related to the use of this product.
References:
1. van der Valk J. Fetal bovine serum (FBS): Past – present – future. ALTEX [Internet]. 2018 [cited 2022 Jan 29];35(1):99–118. Available from: https://pubmed.ncbi.nlm.nih.gov/28800376/
2. van der Valk J, Gstraunthaler G. Fetal Bovine Serum (FBS) – A pain in the dish? Altern Lab Anim [Internet]. 2017;45(6):329–32. Available from: http://dx.doi.org/10.1177/026119291704500611
3. van der Valk J, Mellor D, Brands R, Fischer R, Gruber F, Gstraunthaler G, et al. The humane collection of fetal bovine serum and possibilities for serum-free cell and tissue culture. Toxicol In Vitro [Internet]. 2004 [cited 2022 Jan 29];18(1):1–12. Available from: https://pubmed.ncbi.nlm.nih.gov/14630056/
4. Baker M. Reproducibility: Respect your cells! Nature [Internet]. 2016 [cited 2022 Jan 29];537(7620):433–5. Available from: https://www.nature.com/articles/537433a
Article written in June, 2022
Imperial Bioscience Review 