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A Severe Case of Fraudulent Blending of Fetal Bovine Serum Strengthens the Case for Serum-free Cell and Tissue Culture Applications

In 2011, GE Healthcare (a unit of General Electric
Co.) acquired PAA Laboratories, Linz, Austria. In
April 2013, GE Healthcare published a product
information to customers, stating that batches of
fetal bovine serum (FBS) produced at PAA facili-
ties from March 2008 to March 2013 are subject to
label non-conformances, i.e. that:
“These products may contain added adult bovine
serum albumin (BSA) of United States origin,
water, and/or cell growth promoting additives. For
FBS product shipped into countries other than the
United States, current product labeling states that
the origin of the product is either Australia or EU
approved serum sources. In addition to, or instead
of product of this origin, the product may contain
adult BSA of United States origin and/or may
contain FBS from sources including United States,
Canada, Argentina, Brazil, and/or Mexico.”
This warning of GE Healthcare about the purity
and quality of FBS from PAA Laboratories
prompted us to write a note to inform and to alert
the cell culture community, and to provide back-
ground information about FBS, and about serum
alternatives and serum-free cell culture applica -
tions, respectively.
FBS is a natural cocktail of most of the factors
required for cell attachment, growth and prolifera-
tion, effective for most types of human and animal
(including insect) cells.
Although in use as a
universal growth supplement of cell and tissue
culture media for more than 50 years, FBS has
never been fully characterised. Recent proteomic
and metabolomic studies revealed approximately
1,800 different proteins
and more than 4,000
metabolites present in serum,
with the proportions
of each of these components varying between
different serum batches. Furthermore, global
supply and availability of FBS has changed dramat-
ically over the past few years. FBS is a by-product of
the beef packing industry. Thus, FBS supply is
dictated by many factors, including beef consump-
tion (e.g. more white meat over red meat), feed
prices, environmental factors such as drought,
cattle import and export, governmental farm poli-
and the outbreak of diseases (e.g. foot and
mouth disease, BSE).
From this, it can be concluded that the use of
serum in cell culture may involve a number of
disadvantages: a) serum in general is an ill-defined
supplement in culture media, with high qualitative
and quantitative, geographical and seasonal batch-
to-batch variations; b) FBS may contain adverse
factors, like endotoxins, mycoplasma, viral
contaminants or prion proteins; c) there are animal
welfare concerns surrounding the harvest and
collection of FBS from unborn bovine fetuses; and
d) FBS availability is dependent on the global
There is a severe geographical mismatch between
the supply of, and the demand for, FBS. Demand is
highest in the USA and Europe, while the major
sources of FBS are far away from these areas — in
Brazil, Argentina, South Africa, Australia, New
Zealand, and Central America. It is in these coun-
tries that huge meat cattle herds — bulls and cows
— roam freely together, and as a result, many cows
are pregnant at the time of slaughter.
The same
holds for the geographical distances between raw
serum producers and FBS processors. The latter are
also mainly located in the USA and in Europe. It is
estimated that approximately 500,000 litres of FBS
are sold per year, which means that more than
1,000,000 unborn bovine fetuses have to be
subjected to the harvesting procedure — a fact that
raises major animal welfare concerns,
indeed the numbers are still increasing. As a conse-
quence, a number of strategies were developed in
terms of the Three Rs,
to reduce or replace the
requirement for FBS in cell culture media.
As well as concerns about the number of animals
required to supply the FBS market, there are addi-
tional concerns that this market is only loosely
— and this creates opportunities for
This abuse has been evident in the
past, and is most likely still happening now. For
example, in 1994 it was reported
that approxi-
mately 30,000 litres of “New Zealand” FBS was
sold worldwide. However, only 15,000 litres of
high-quality FBS were annually collected in New
Zealand. Even now, exact figures for the global
FBS production rate are still unavailable, which
raises suspicions as to whether FBS in general
might be blended with other sera to meet
increasing demands. No attempts have ever been
ATLA 42, 207–209, 2014 207
A Severe Case of Fraudulent Blending of Fetal Bovine
Serum Strengthens the Case for Serum-free Cell and
Tissue Culture Applications
undertaken to trace the collected sera, in order to
gain clear evidence about their geographical
Obviously, in the last 20 years nothing has
As pointed out above, many FBS
batches were blended with bovine serum albumin,
water and growth promoting additives.
The US
Food and Drug Administration (FDA) reports that
143 batches of FBS, amounting to a total of approx-
imately 280,000 litres, are affected.
This latest
incident might be just the tip of the iceberg. Most
importantly, the actual case might also have a
substantial impact on many thousands of cell and
tissue culture experiments, and, in particular,
where GLP and GMP conditions are required, this
can hardly be ignored!
This recent fraudulent action should be taken as
an opportunity to question the use of FBS as cell
culture media supplement. We therefore appeal to
cell and tissue culturists to reduce or completely
avoid FBS in their cultures, and to turn to other
options, e.g. serum-free cell and tissue culture,
or the replacement of FBS by the use of serum
substitutes, such as human platelet lysates.
particular, cultures that are newly initiated should
be grown from the very beginning under serum-free
conditions. In 2003 and 2009, European cell culture
experts gathered at two workshops to discuss
options for, and the methodologies of, serum-free cell
culture. Two comprehensive workshop reports were
in which clear recommendations for
the replacement of FBS, and for the design of serum-
free media, respectively, are provided. Following
these report recommendations will result in:
scientifically better (and more-reproducible) data;
safer products;
ethical research without harming animals;
better availability of cell and tissue culture
the transparent and traceable composition of
culture media; and
a significant contribution to Good Cell Culture
Professor Gerhard Gstraunthaler
Division of Physiology
Innsbruck Medical University
Professor Toni Lindl
Institut für Angewandte Zellkultur
Dr Jan van der Valk
3Rs-Centre Utrecht Life Sciences
Utrecht University
The Netherlands
Gstraunthaler, G., Lindl, T. & van der Valk, J. (2013).
A plea to reduce or replace fetal bovine serum in cell
culture media. Cytotechnology 65, 791–793.
Gstraunthaler, G. & Lindl, T. (2013). Zell- und
Gewebekultur. 7th edition, 340pp. Heidelberg, Germ -
any: Springer Spektrum Verlag.
Anderson, N.L. & Anderson, N.G. (2002). The human
plasma proteome. History, character, and diagnostic
prospects. Molecular & Cellular Proteomics 1,
Anderson, N.L., Polanski, M., Pieper, R., Gatlin, T.,
Tirumalai, R.S., Conrads, T.P., Veenstra, T.D.,
Adkins, J.N., Pounds, J.G., Fagan, R. & Lobley, A.
(2004). The human plasma proteome: A non-redun-
dant list developed by combination of four separate
sources. Molecular & Cellular Proteomics 3, 311–326.
Psychogios, N., Hau, D.D., Peng, J., Guo, A.C.,
Mandal, R., Bouatra, S., Sinelnikov, I., Krish na -
murthy, R., Eisner, R., Gautam, B., Young, N., Xia, J.,
Knox, C., Dong, E., Huang, P., Hollander, Z.,
Pedersen, T.L., Smith, S.R., Bamforth, F., Greiner, R.,
McManus, B., Newman, J.W., Goodfriend, T. &
Wishart, D.S. (2011). The human serum metabolome.
PloS One 6, e16957.
Shailer, C. & Corrin, K. (1999). Serum supply: Policies
and controls operating in New Zealand. Developments
in Biological Standardization 99, 71–77.
Asher, D.M. (1999). Bovine sera used in the manufac-
ture of biologicals: Current concerns and policies of
the U.S. Food and Drug Administration regarding the
transmissible spongiform encephalopathies. Develop -
ments in Biological Standardization 99, 41–44.
Dormont, D. (1999). Transmissible spongiform
enceph alopathy agents and animal sera. Develop -
ments in Biological Standardization 99, 25–34.
Even, M.S., Sandusky, C.B. & Barnard, N.D. (2006).
Serum-free hybridoma culture: Ethical, scientific and
safety considerations. Trends in Biotechnology 24,
Wessmann, S.J. & Levings, R.L. (1999). Benefits and
risks due to animal serum used in cell culture produc-
tion. Developments in Biological Standardization 99,
Brindley, D.A., Davie, N.L., Culme-Seymor, E.J.,
Mason, C., Smith, D.W. & Rowley, J.A. (2012). Peak
serum: Implications of serum supply for cell therapy
manufacturing. Regenerative Medicine 7, 7–13.
Fujimoto, B. (2002). Fetal bovine serum — Supply vs
demand? Art to Science 21, 1–4.
Jochems, C.E., van der Valk, J.B.F., Stafleu, F.R. &
Baumans, V. (2002). The use of fetal bovine serum:
Ethical or scientific problem? ATLA 30, 219–227.
Brunner, D., Frank, J., Appl, H., Schöffl, H., Pfaller,
W. & Gstraunthaler, G. (2010). Serum-free cell
culture: The serum-free media interactive online data-
base. ALTEX 27, 53–62.
van der Valk, J., Brunner, D., De Smet, K., Fex
Svenningsen, Å., Honegger, P., Knudsen, L.E., Lindl,
T., Noraberg, J., Price, A., Scarino, M.L. & Gstraun -
208 Comment
thaler, G. (2010). Optimization of chemically defined
cell culture media — Replacing fetal bovine serum in
mammalian in vitro methods. Toxicology in Vitro 24,
van der Valk, J., Mellor, D., Brands, R., Fischer, R.,
Gruber, F., Gstraunthaler, G., Hellebrekers, L.,
Hyllner, J., Jonker, F.H., Prieto, P., Thalen, M. &
Baumans, V. (2004). The humane collection of fetal
bovine serum and possibilities for serum-free cell and
tissue culture. Toxicology in Vitro 18, 1–12.
Balls, M., Goldberg, A.M., Fentem, J.H., Broadhead,
C.L., Burch, R.L., Festing, M.F.W., Frazier, J.M.,
Hendriksen, C.F.M., Jennings, M., van der Kamp,
M.D.O., Morton, D.B., Rowan, A.N., Russell, C.,
Russell, W.M.S., Spielmann, H., Stephens, M.L.,
Stokes, W.S., Straughan, D.W., Yager, J.D., Zurlo, J.
& van Zutphen, B.F.M. (1995). The Three Rs: The way
forward. The report and recommendations of ECVAM
Workshop 11. ATLA 23, 838–866.
Hodgson, J. (1991). Checking the sources: The serum
supply secret. Nature Biotechnology 9, 1320–1324.
Hodgson, J. (1993). Fetal bovine serum revisited.
Nature Biotechnology 11, 49–53.
Hodgson, J. (1995). To treat or not to treat: That is the
question for serum. Nature Biotechnology 13, 333–
Nielsen, O. (1995). Changing serum’s mind-set.
Nature Biotechnology 13, 626.
Bohn, B. (1995). Fatal bovine serum. Nature Bio -
technology 13, 926–927.
FDA (2013). Class 2 Device Recall GE Healthcare/
PAA Healthcare. Silver Spring, MD, USA: US Food
and Drug Administration. Available at: http://www.
ID=117863 (Accessed 02.04.14).
Gstraunthaler, G. (2003). Alternatives to the use of
fetal bovine serum: Serum-free cell culture. ALTEX
20, 275–281.
Bieback, K. (2013). Platelet lysate as replacement for
fetal bovine serum in mesenchymal stromal cell
cultures. Transfusion Medicine & Hemotherapy 40,
Rauch, C., Feifel, E., Amann, E-M., Spötl, H.P., Schen -
nach, H., Pfaller, W. & Gstraunthaler, G. (2011).
Alternatives to the use of fetal bovine serum: Human
platelet lysates as a serum substitute in cell culture
media. ALTEX 28, 305–316.
Rauch, C., Wechselberger, J., Feifel, E. & Gstraun -
thaler, G. (2014). Human platelet lysates successfully
replace fetal bovine serum in adipose-derived adult
stem cell culture. Journal of Advanced Biotechnology &
Bioengineering 2, 1–11.
Coecke, S., Balls, M., Bowe, G., Davis, J., Gstraun -
thaler, G., Hartung, T., Hay, R., Merten, O.W., Price,
A., Schechtman, L., Stacey, G. & Stokes, W. (2005).
Guidance on Good Cell Culture Practice. A report of
the second ECVAM task force on Good Cell Culture
Practice. ATLA 33, 261–287.
Comment 209
... In 1994, 30,000 L of FBS were documented to be sourced from New Zealand; however, the country itself only reported a 15,000 L annual production (van der Valk et al., 2017). A second major adulteration case in 2013 was documented with the dilution of FBS with bovine albumin, water, and other growth-promoting substances by a major global supplier (Gstraunthaler, Lindl, & van der Valk, 2014). Investigations by the Food and Drug Administration concluded that ∼280,000 L of FBS were affected between 2008 and 2013 (Gstraunthaler et al., 2014). ...
... A second major adulteration case in 2013 was documented with the dilution of FBS with bovine albumin, water, and other growth-promoting substances by a major global supplier (Gstraunthaler, Lindl, & van der Valk, 2014). Investigations by the Food and Drug Administration concluded that ∼280,000 L of FBS were affected between 2008 and 2013 (Gstraunthaler et al., 2014). In addition, animal products could potentially contain undesirable or dangerous adventitious agents, which is a safety concern of using FBS in vaccine manufacturing. ...
Full-text available
Vaccines provide effective protection against many infectious diseases as well as therapeutics for select pathologies, such as cancer. Many viral vaccines require amplification of virus in cell cultures during manufacture. Traditionally, cell cultures, such as VERO, have been used for virus production in bovine serum‐containing culture media. However, due to concerns of potential adventitious agents present in fetal bovine serum (FBS), regulatory agencies suggest avoiding the use of bovine serum in vaccine production. Current serum‐free media suitable for VERO‐based virus production contains high concentrations of undefined plant hydrolysates. Although these media have been extensively used, the lack of chemical definition has potential to adversely affect cell growth kinetics and subsequent virus production. As plant hydrolysates are made from plant raw materials, performance variations could be significant among different lots of production. We developed a chemically defined, serum‐free medium, OptiVERO, that was optimized specifically for VERO cells. VERO cell growth kinetics were demonstrated to be equivalent to EMEM‐10% FBS in this chemically defined medium while the plant hydrolysate‐containing medium demonstrated a slower doubling time in both 2D and 3D cultures. Virus production comparisons demonstrated that the chemically defined OptiVERO medium performed at least as good as the EMEM‐10%FBS and better than the plant hydrolysate‐containing media. We report the success in using recombinant proteins to replace undefined plant hydrolysates to formulate a chemically defined medium that can efficiently support VERO cell expansion and virus production. This article is protected by copyright. All rights reserved.
... The FBS batch 'Serum A' may have been involved in undeclared blending with bovine serum albumin (BSA) (Gstraunthaler et al., 2014). BSA can act protectively when involved in nanoparticle-cell interactions (Gualtieri et al., 2012;Peuschel et al., 2015). ...
... trypsin)are animal-derived. Ethical issues with animal-derived components, especially FBS, have been discussed for years [4][5][6][7][8][9][10][11] and still continue to spark debate. 12,13 Techniques that aim to replace procedures on live animals should be animal component-free, in order to avoid collateral animal suffering. ...
Cell culture techniques are strongly connected with modern scientific laboratories and production facilities. Thus, choosing the most suitable medium for the cells involved is vital, not only directly to optimise cell viability but also indirectly to maximise the reliability of the experiments performed with the cells. Fetal bovine or calf serum (FBS or FCS, respectively) is the most commonly used cell culture medium supplement, providing various nutritional factors and macromolecules essential for cell growth. Yet, the use of FBS encompasses a number of disadvantages. Scientifically, one of the most severe disadvantages is the lot-to-lot variability of animal sera that hampers reproducibility. Therefore, transitioning from the use of these ill-defined, component-variable, inconsistent, xenogenic, ethically questionable and even potentially infectious media supplements, is key to achieving better data reproducibility and thus better science. To demonstrate that the transition to animal component-free cell culture is possible and achievable, we highlight three different scenarios and provide some case studies of each, namely: i) the adaptation of single cell lines to animal component-free culture conditions by the replacement of FBS and trypsin; ii) the adaptation of multicellular models to FBS-free conditions; and (iii) the replacement of FBS with human platelet lysate (hPL) for the generation of primary stem/stromal cell cultures for clinical purposes. By highlighting these examples, we aim to foster and support the global movement towards more consistent science and provide evidence that it is indeed possible to step out of the currently smouldering scientific reproducibility crisis.
... This emphasizes the variability that can occur in FBS production. Gstraunthaler et al. (32) stated that variability is driven by poor regulations on FBS production. What begins as a practical problem for the successful in vitro culture of MSCs can turn into commercial and clinical problems in that FBS batch-tobatch variability may also lead to an inconsistent cellular product over the long-term. ...
Full-text available
Fetal bovine serum (FBS) remains widely used as a supplement in cell culture media used in the isolation and expansion of mesenchymal stromal cells (MSC) despite longstanding practical, clinical, and ethical concerns over its use. As a result, research on alternative culture media supplement solutions that conserve crucial MSC characteristics has become increasingly relevant. Species-specific supplements and serum-free media such as platelet lysate or chemically defined media have been assessed for their effect in MSC cultures regarding proliferation, differentiation, and immunomodulatory capacity. While none of the alternatives offer a complete solution in replacing traditional FBS supplemented media for culturing MSCs for all species, short-term or transitional use of FBS-free media can perform equally well and could address some of the concerns over the use of FBS.
... Apart from the ethical concerns, the absence of full characterization, batch to batch variation, and contamination were documented by Piletz et al. (2018), among others. Furthermore, Gstraunthaler et al. reported fraudulent blending of FBS in 2014 (Gstraunthaler et al., 2014). A chapter on culture media was written by Burgener and Butler (Burgener et al., 2006) and is highly recommended. ...
The discipline of microphysiometry emerged at the end of the 1980s and has been progressing towards today's organs on chips and microphysiological systems approaches. The presented work reviews the development of cellular model from cellular monolayers toward 3D multi-cellular tissue constructs, along with the maturation of sensor principles and technologies. A modular classification into cellular models, biochip, climate control and fluidic system, and control & data acquisition is introduced. The experimental conditions and aspects of data processing are discussed and reproducibility issues such as the use of chemically defined cell culture medium are addressed. A brief review of applications and an outlook on current challenges in the field conclude the review paper.
... The Food and Drug Administration (FDA) of the USA pointed out that there is nearly 28 thousand litres of FBS in 143 batches which were effected [38]. There is still not any betterment in the situation till 2014 regarding FBS quality [39]. ...
Full-text available
With the advances in regenerative medicine, research is focused towards biologically safe alternatives to cure pathologies. For this purpose, stem cells are potential candidates. An essential component of stem cell culture media is Fetal Bovine Serum (FBS) which provides necessary growth factors and hormones. Unfortunately, there is an increasing concern about quality of FBS as there are reports of adulteration and route of FBS origin and transportation is not fully traceable. Alternatively, Platelet-Rich Plasma (PRP), an autologous preparation, is used in stem cell culture as it provides similar growth factors as that of FBS. Though, the results with the use of PRP show varying degree of success, still it is getting popular among the cell culturing community because of ease of access, cheaper cost and promising response. In this review, we have described limitation in use of FBS in stem cell culture, preparation and potential of PRP as well as comparative behaviour of mesenchymal stem cells (MSCs) in terms of their stemness, proliferation, differentiation and immunoregulatory properties in both cell culture media components i.e. FBS and PRP.
... 9 In this context, it is worth noting that cases of fraudulent FBS diluted with adult bovine serum albumin (BSA) reaching the market have been reported in the past, and there were many suspicious mismatches over the years between the actual volumes of FBS produced in certain countries and the volumes sold under their label globally. 13 In an attempt to avoid the many drawbacks associated with the use of FBS, serum-free and xeno-free supplements have been developed for cell culture. 11 While chemically defined media reduce the batch-to-batch variability of cell culture, the removal of albumin and other bulk serum proteins narrows the spectrum of cells whose growth they support. ...
Virus safety of fetal bovine serum (FBS) is a critical issue for cell culture and clinical applications of cell therapies. The size exclusion filtration of FBS-supplemented cell culture media through small-size virus retentive filter paper is presented to investigate its effect on cell culture. A substantial proportion of proteins (ca. 45%) was removed by nanofiltration, yet important transport proteins (albumin, fetuins, macroglobulins, transferrin) were unaffected. The cell viability of Chinese hamster ovary (CHO) and human embryonic kidney 293 (HEK-293) cells that were grown in media supplemented with nanofiltered FBS was surprisingly high, despite the observed protein losses. Protein depletion following nanofiltration resulted in detectable levels of autophagy markers.
Full-text available
Fetal bovine serum (FBS) is a widely used growth supplement in the in vitro culturing of animal and human cells, tissues and organs, notably due to the occurrence of abundant micro- and macronutrients, along with growth factors. Over the years, increasing demand, high price, batch-to-batch variability in quality and composition, increasing ethical concerns lead to the search for an alternative to FBS. Several approaches have been suggested and employed in the past, but none is implemented as widely as FBS, and each supplement has its own disadvantages. In this review, we described the importance of FBS in cell culture, discussed the issues associated with FBS use and presented the efforts made in the recent past to reduce or replace FBS. The potential of four different alternative sources to FBS, namely, bovine ocular fluid, sericin protein, human platelet lysate and earthworm heat inactivated coelomic fluid was evaluated. In the end, we present the conceptual perspective using the Human Platelet Lysate (HPL) and earthworm Heat Inactivated Coelomic Fluid (HI-CF) combination to alternate FBS and its context in scientific and economic impacts.
In der FrühphaseMediumder ZellZellkulturmediumMedium- und GewebekulturKulturmediumMedium wurden zur Anzucht der Gewebeexplantate ausschließlich biologische Flüssigkeiten, wie Gerinnsel aus Froschlymphe, Plasmagerinnsel, Embryonalextrakte, u. Ä. verwendet (s. Einleitung).
Full-text available
Objective Currently the replacement of fetal calf serum (FCS) by a more suitable alternative is a sought aim in the field of tissue and cell culture research. Autologous plasma (AP) and especially autologous serum (AS) have been shown to be effective substitutes of FCS in culture media for some of cell types. Nevertheless, there is no comparative data on the most appropriate supplement for cell media in neutrophil studies, it is now unclear whether AP have relatively an equal, superior or inferior performance to FCS in neutrophil cell culture. In the present study, human blood neutrophils were isolated and cultured in FCS- or AP-supplemented medium. After 12, 36 and 60 hours of incubation, cell viability, oxidative burst and CD11b expression were determined by flow cytometry.Results Compared to the culture of neutrophils in FCS 10% medium, the culture of neutrophils in a medium with AP 10% could prolong their life span without affecting their function. The findings introduce AP as a better supplement for human neutrophil cell culture than FCS and propose a simple and economical procedure for neutrophil isolation and culture.
Full-text available
Fetal bovine serum (FBS) is still the gold standard as a cell culture medium additive due to its high level of growth stimulatory factors. Although supplementation of growth media with FBS is common practice in cell and tissue culture, FBS bears a number of disadvantages and its use has been questioned recently: (1) an ill-defined medium supplement, (2) qualitative and quantitative batch-to-batch variations, and (3) animal welfare concerns regarding the harvest of bovine fetal blood. Recently, we were able to show the capacity of human platelet -granule lysates to replace FBS in a variety of human and animal cell culture systems. Thus, lysates of human donor platelets may become a valuable non animal-derived substitute for FBS in cultures of mammalian cells and in human and animal stem cell technology. Stem cells may become the future for human-based alternative to animal testing, in vitro toxicology, and drug safety assessment. New stem cell-based test systems are continuously established, and their performance under animal-derived component free culture conditions has to be defined in prevalidation and validation studies. In order to accomplish these tasks, adipose-derived mesenchymal stem cells (ADSC) were expanded in media supplemented with platelet lysates. Proliferation assays by resazurin and WST-8 compared with direct cell counting confirmed the growth promoting effect of platelet lysate, comparable to high FBS. Furthermore, we established culture conditions that ADSC kept their undifferentiated state as determined by CD73, CD90 and CD105 expression and the lack of negative marker CD45. Preliminary tests whether ADSC can be differentiated towards adipogenic, osteogenic, or chondrogenic phenotypes under platelet lysate supplemented growth conditions were also successful.
Full-text available
The search for alternatives to the use of fetal bovine serum (FBS) in cell and tissue culture media has become a major goal in terms of the 3R principles in order to reduce or to avoid harvesting of FBS from bovine fetuses, and, in terms of Good Manufacturing Practice (GMP), to ensure safe and animal product-free conditions for biomedical tissue engineering and (adult) stem cell therapy, respectively. In the present study, we investigated the feasibility of using platelet lysates (PL) as a substitute for FBS, based on the fact that most of the potent mitogenic factors present in serum are derived from activated thrombocytes. Platelet lysates were obtained from outdated human donor platelet concentrates. Methods were established to activate human donor platelets in order to achieve a maximum yield of platelet a-granule growth factors. Platelet lysates were successfully introduced to grow and maintain anchorage-dependent and -independent human and animal cell lines. For cell culture experiments, cells were either grown in culture media supplemented with 10% FBS, 5% PL, or under serum-free conditions. Growth experiments, viability assays, and platelet lysate-induced activation of ERK1/2 mitogen-activated protein kinase revealed platelet lysates as a valuable alternative to FBS in cell culture media.
Pflanzliche Zell- und Gewebekulturen sind zu einem wichtigen Hilfsmittel der Grundlagenforschung und der praktischen Pflanzenzüchtung geworden, da ihre Relevanz für die Biotechnologie und die Agrarwirtschaft erkannt worden ist (Abb. 23-1a, Abb. 23-1b).
Mesenchymal stromal cells (MSC) emerged as highly attractive in cell-based regenerative medicine. Initially thought to provide cells capable of differentiation towards mesenchymal cell types (osteoblasts, chondrocytes, adipocytes etc.), by and by potent immunoregulatory and pro-regenerative activities have been discovered, broadening the field of potential applications from bone and cartilage regeneration to wound healing and treatment of autoimmune diseases. Due to the limited frequency in most tissue sources, ex vivo expansion of MSC is required compliant with good manufacturing practice (GMP) guidelines to yield clinically relevant cell doses. Though, still most manufacturing protocols use fetal bovine serum (FBS) as cell culture supplement to isolate and to expand MSC. However, the high lot-to-lot variability as well as risk of contamination and immunization call for xenogenic-free culture conditions. In terms of standardization, chemically defined media appear as the ultimate achievement. Since these media need to maintain all key cellular and therapy-relevant features of MSC, the development of chemically defined media is still - albeit highly investigated - only in its beginning. The current alternatives to FBS rely on human blood-derived components: plasma, serum, umbilical cord blood serum, and platelet derivatives like platelet lysate. Focusing on quality aspects, the latter will be addressed within this review.
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A year ago serum regulations were a hodgepodge. Has anything changed?