Abstract
The supplementation of culture medium with fetal bovine serum (FBS, also referred to as "fetal calf serum") is still common practice in cell culture applications. Due to a number of disadvantages in terms of quality and reproducibility of in vitro data, animal welfare concerns, and in light of recent cases of fraudulent marketing, the search for alternatives and the development of serum-free medium formulations has gained global attention. Here, we report on the 3rd Workshop on FBS, Serum Alternatives and Serum-free Media, where regulatory aspects, the serum dilemma, alternatives to FBS, case-studies of serum-free in vitro applications, and the establishment of serum-free databases were discussed. The whole process of obtaining blood from a living calf fetus to using the FBS produced from it for scientific purposes is de facto not yet legally regulated despite the existing EU-Directive 2010/63/EU on the use of animals for scientific purposes. Together with the above-mentioned challenges, several strategies have been developed to reduce or replace FBS in cell culture media in terms of the 3Rs (Refinement, Reduction, Replacement). Most recently, releasates of activated human donor thrombocytes (human platelet lysates) have been shown to be one of the most promising serum alternatives when chemically-defined media are not yet an option. Additionally, new developments in cell-based assay techniques, advanced organ-on-chip and microphysiological systems are covered in this report. Chemically-defined serum-free media are shown to be the ultimate goal for the majority of culture systems, and examples are discussed.
Highlights
1.1 Workshops on the replacement of FBS This is the report of the 3rd workshop devoted to the replacement of fetal bovine serum (FBS) in cell and tissue culture methods
The first widespread use of serum-free medium was developed for primary neuronal cultures to more closely approximate cerebrospinal fluid (CSF), which normally contains less than 0.001% protein compared to approximately 8% in serum (Busher, 1990)
From an animal welfare point of view, the current practice of obtaining FBS is unacceptable because of the potential suffering the fetuses might experience during the entire process
Summary
1.1 Workshops on the replacement of FBS This is the report of the 3rd workshop devoted to the replacement of fetal bovine serum (FBS) in cell and tissue culture methods. A second workshop was organized in Copenhagen, Denmark, in 2009 to discuss current in vitro methods devoid of FBS or other animal components and strategies to develop serum-free media (van der Valk et al, 2010). Owing to the questionable reproducibility of models that rely on FBS, their use for regulatory purposes is debated (Brindley et al, 2012; Mannello and Tonti, 2007; Tekkatte et al, 2011) For this reason, serum-supplemented media should be avoided wherever possible, and chemically-defined media preferred (see Section 2, and van der Valk et al, 2010). Safety, scientific, and ethical aspects are incentives to develop and use (fetal bovine) serum-free media
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