Future Foods 3 (2021) 100032

Contents lists available at ScienceDirect

Future Foods
journal homepage: www.elsevier.com/locate/fufo

Trends and ideas in technology, regulation and public acceptance of

cultured meat
Xin Guan a,b,c,d, Qingzi Lei a,b,c, Qiyang Yan a,b, Xueliang Li a,b, Jingwen Zhou a,b,c,d,
Guocheng Du a,b,∗, Jian Chen a,b,c,d,∗
a
Science Center for Future Foods, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China
b
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China
c
National Engineering Laboratory for Cereal Fermentation Technology (NELCF), Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China
d
Jiangsu Provisional Research Center for Bioactive Product Processing Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China

a r t i c l e i n f o a b s t r a c t

Keywords: As future foods, cultured meat is produced by culturing animal cells ex vivo rather than raising and slaughtering
Cultured meat animals. It is a promising way to address concerns about resource consumption, environmental pollution, public
Muscle tissue healthy that associated with conventional livestock production. In the past two years, dozens of cultured meat-
Large-scale manufacturing
related start-ups have been founded and millions of dollars have been raised, demonstrating the high business
Cost reduction
enthusiasm, broad market prospects and high profitability expected. However, currently many startups are yet
Animal component-free medium
Capital investment determining, optimizing steps of the process or trying to scale-up, so it is still a very long way before cultured meat
becomes comparable to the conventional meat. Here, we review the industry status of cultured meat around the
world from the geographical distribution, potential products, and funding landscape and, identify the advanced
technologies in large-scale manufacturing of cultured meat covering aspects from culture medium optimization,
bioreactor designation, scaffold fabrication and cost reduction. Moreover, we discuss the challenges related to
policy formulation and public acceptance of cultured meat.

1. Introduction
The first challenge for humanity today is feeding 10 billion people
by 2050 (UNPD, 2019). As one of the most important food resources
and nutrients for the clear majority of people, meat has already been
consumed over 300 million tons in 2014 and a 76% of growth by 2050
is predicted (Alexandratos and Bruinsma, 2012). The traditional way
of meat production is to breed, raise and slaughter whole animals,
which takes a relatively long period, consumes large water and land
resources, uses a large amount of fuel energy, and causes severe envi-
ronment pollution. (FAO, 2006; Gerber et al., 2013; Herrero et al., 2011;
Hoekstra and Mekonnen, 2012). In addition, the epidemics of African
swine fever, avian flu and other animal diseases have brought more un-
certain factor to the conventional livestock production (Dixon et al.,
2020; Normile, 2008; Taylor et al., 2019). Therefore, it is urgent to de-
velop high-efficient, eco-friendly and sustainable meat production strat-
egy.
As one of the “Top 10 Emerging Technologies of 2018″ published
by the World Economic Forum, cultured meat has been considered as a
promising solution to mitigate concerns related to livestock agriculture
(Cann, 2018; Jiang et al., 2020; Lee et al., 2020). Cultured meat is also
called lab-grown meat, which is produced by ex vivo culture of animal
cells by utilizing the operation techniques in the field of cell biology,
tissue and food engineering (Post, 2012). Generally, stem cells which
have the potential of self-renewal and multiple differentiation are iso-
lated from an animal biopsy, and then expanded and differentiated ex
vivo to generate muscle fibers, fat or other cell types that make up muscle
tissue. Subsequently, these cells are collected and assembled to form ed-
ible meat end-products after food processing such as molding, coloring
and seasoning (Arshad et al., 2017; Datar and Betti, 2010; Kadim et al.,
2015). Therefore, cultured meat technology intends to directly produce
meat by ex vivo cell culture and no extensive animal raising and slaugh-
tering are required, making it a novel and promising meat production
technology. Much more importantly, cultured meat technology would
greatly shorten the meat production cycles, reduce the consumption of
lands, water, and energy, and curb greenhouse gas emissions (Tuomisto
and de Mattos, 2011).
As early as the 1930s, British Minister Winston Churchill proposed
the idea of eating meat by culturing individual tissues in medium rather
than raising the entire animals (Churchill, 1932). This can be regarded

∗
Corresponding authors at: Science Center for Future Foods, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
E-mail addresses: gcdu@jiangnan.edu.cn (G. Du), jchen@jiangnan.edu.cn (J. Chen).

https://doi.org/10.1016/j.fufo.2021.100032
Received 28 December 2020; Received in revised form 16 February 2021; Accepted 24 March 2021
2666-8335/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)
X. Guan, Q. Lei, Q. Yan et al.
as the rudiment of cultured meat, but in terms of the science and tech-
nology at that time, cultured meat was just a fantasy and vision of the
future. It was at the beginning of the 21st century that research on
cultured meat began and burgeoned. Since 2002, National Aeronautics
and Space Administration (NASA) funded research to produce cultured
turkey and golden fish meat, creating the first edible cultured turkey
strips (Edelman et al., 2005) and fish fillet (Benjaminson et al., 2002). In
2013, professor Mark Post launched the world’s first cultured beef ham-
burger after years of research, which is made up of more than 10,000
muscle fibers and costs nearly $330,000 (Post, 2014). Although the high
cost, the success of cultured meat technology triggered great attention
of people from all walks of life, including scientists, entrepreneurs and
investors. Since then, numerous companies have been founded to de-
velop cultured meat products and have get access to capital, promoting
the explosion of cultured meat industry.
Because of the immature production process and high production
cost, cultured meat is currently in its infancy, and researchers are fran-
tically working on technological improvement to speed up the indus-
trialization and commercialization process of cultured meat. This re-
view summarizes current cultured meat-related star-ups and discusses
the challenges for the commercialization of cultured meat at technol-
ogy, regulation and customer levels. Meanwhile, further research focus
and potential strategies for the production and marketing of cultured
meat are also put forward accordingly.
2. The blooming cultured meat industry
Since the first cultured beef hamburger was produced in 2013,
dozens of companies have get into the cultured meat industry and var-
ious product species such as chicken, beef, pork, and seafood are in
the development process. By the end of 2020, approximately 60 early-
stage companies have been set up in the worldwide, focusing on cul-
tured meat end-products, raw materials or equipment along the value
chain, and more than half of them launched within the past 2 years
(Choudhury et al., 2020; GFI, 2020). The geographical distribution
of these companies is in 19 countries across five continents, 37% in
North America, 25% in Asia, and 21% in Europe (Fig. 1). From 2016
to 2020, the total amount of capital invested in cultured meat compa-
nies reaches approximately $460 million with over 3 quarters-more than
$350 million-closing in 2019 and 2020 (Fig. 2A). Among them, Memphis
Meat has raised approximately $200 million to achieve the leader posi-
tion and Mosa Meat is the second with received over $85 million. These
two companies account for more than half of total capital in the cultured
meat industry (Fig. 2B). It is worth noting that nine companies have
raised their Series A/B fundraising rounds in 2020, indicating growing
mainstream investor interest and gradually mature industry stage.
In terms of the product interest, 28% of cultured meat companies
focus on cultured beef and pork, 12% of companies are interested in
seafood, 10% of companies are interested in poultry, and 28% of com-
panies do not focus on final products but raw materials or equipment in
the production process (Fig. 3). Interestingly, potential product choices
by companies show obvious regional differences, greatly influenced by
local dietary habits and customs. In specific, cultured fish maw will be
launched by a Hong Kong company because in southern China fish maw
is often consumed in soup with credited properties of beautifying skin
and anti-aging (Siu, 2019). Three companies in Europe and Japan intend
to produce cultured foie gras due to its unique position in their food cul-
ture (Southey, 2020; Webber, 2019). Likewise, cultured kangaroo will
be offered by an Australian company (Upshall, 2021). In addition, plenty
of business to business companies emerge to embrace the whole cul-
tured meat value chain, including low-cost cell culture medium, biore-
actor, scaffolding materials, and cell lines. So far there are at least three
companies announcing to produce and sell cultured meat products in
2021, and more products will come to market in the next five years
(Fusaro, 2021; Lucas, 2020; Webber, 2019).
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Future Foods 3 (2021) 100032
3. Main production process of cultured meat
The production process of cultured meat is a set of tissue and food
engineering processes used to create a food product, which can be briefly
divided into four key steps: (1) acquisition of seed cells, (2) large-scale
expansion of seed cells, (3) induced differentiation of seed cells into
myofibers, adipocytes, or other mature cell types in muscle tissues, and
(4) assembly and food processing of all cultured cells into meat products
(Fig. 4).
Step 1: Seed cells are animal cells that can vigorously proliferate
and efficiently generate to myoblasts, adipocytes, and other cell types
that compose muscle tissue, usually referring to stem cells. Embryonic
stem cells, induced pluripotent stem cells, muscle stem cells, and mes-
enchymal stem cells are potential types of seed cells (Díaz-Flores et al.,
2006; Genovese et al., 2017; Kadim et al., 2015; Williams et al., 2012).
In addition, some adult cells such as fibroblasts can also be operated to
form myoblasts and lipoblasts by transdifferentiation or dedifferentia-
tion (Boularaoui et al., 2018; Oki et al., 2008). In general, these cells can
be efficiently obtained from a biopsy of living animal tissue after isola-
tion via enzymatic digestion and mechanical disruption and purification
via flow sorting with specific surface markers (Ding et al., 2017). Al-
though various cell sources can be used to produce cultured meat, each
cell type needs specific ex vivo expansion and differentiation strategy
according to their growth and development characteristics (Fish et al.,
2020; Stephens et al., 2018; Zhang et al., 2020).
Step 2: Once seed cells are collected, they need to be proliferated to
achieve large cell numbers. The laboratory culture scale with flasks or
dishes is far from satisfying the market demand, so it is necessary to de-
velop a large-scale bioreactor system (Post et al., 2020). Moreover, the
process should use economical serum-free medium, and monitor various
parameters such as pH, dissolved O2 and CO2 , concentration of impor-
tant nutrients and metabolic waste online (Allan et al., 2019). At the
same time, to efficiently utilize resources and keep low production cost,
it is important to conduct the medium recycling with automatic removal
of toxic wastes and replenishment of nutrients based on the monitoring
feedback.
Step 3: When the desired number of cells is achieved, cells are then
induced to differentiate into myotubes, adipocytes, or other mature cell
types in muscle tissues. The maturity level of generated final cells is
a key evaluation index in this step because feature structure and nu-
trient content including proteins, fatty acids, and vitamins are signifi-
cantly affected by cell maturity (Liu, 2019). It is worth noting that al-
though muscle stem cells are generally considered to have strong myo-
genic differentiation potential, the diameter, length and protein content
of ex vivo formed myofibers vary greatly based on the culture condi-
tion and might be much lower than real muscle fibers (Braga et al.,
2017; Lamarche et al., 2021; Park et al., 2016). Therefore, it is impor-
tant to optimize the differentiation condition and increase the maturity
of differentiated cells based on the mechanism of in vivo muscle tissue
development.
Step 4: As the last step of cultured meat production, the obtained
mature cells are collected and processed including molding, color-
ing, and seasoning, ultimately forming the cultured meat end-product
(Zhao et al., 2019). Because conventional cell culture approach can only
form a two-dimensional (2D) thin cell layer, assembly of myofibers,
adipocytes, and maybe connective tissue cells are essential to form a
piece of structured and marbleized meat (Stephens et al., 2018). More-
over, the molding procedure can be merged into Step 3 where various
cell types are co-cultured in a biomimetic three-dimensional (3D) en-
vironment provided by the scaffold or hydrogel (Tuomisto, 2019). Be-
sides, advances in 3D bio-printing technology makes it promising for
creating muscle tissue with relative-large size and complex compos-
ite constructs through elaborate arrangement of cell-laden hydrogels
(Kang et al., 2016). At last, the final product can be achieved after food
processing such as supplementation of heme proteins and seasoning sub-
stances.
X. Guan, Q. Lei, Q. Yan et al.
Fig. 1. Geographic distribution of cultured meat companies. Fifty-eight companies in the field of cultured meat/fish are included, focusing on cultured meat end-
products, raw materials, or equipment along the value chain. More information on these companies is available in GFI’s company database (GFI, 2021).
4. Technical challenges for large-scale production of cultured
meat
Although creating a cellular biomass can be achieved using existing
technology regardless of scale and cost, the product cannot be regarded
as equivalent to a piece of meat if not providing similar texture, flavor
and nutrition content. Therefore, currently the cultured meat industry is
still in its infancy, indicating that each production procedure needs to be
optimized and many technology challenges need to be addressed before
cultured meat products are ready into the ordinary people’s table.
4.1. Animal component-free medium for cell culture
As a cell culture-based products, development of optimal culture
medium is one of the top priorities for cultured meat (Mizukami and
Swiech, 2018). Specifically, the culture medium must not only promote
the efficient proliferation and differentiation of cells, but issues such as
cost and food safety should also be taken into account.
The first challenge is to remove the fetal bovine serum (FBS) and
other animal-derived components from the culture medium. FBS is
an important and universal growth-promoting supplement in animal
cell medium, but it has high price, complicated and unclear compo-
sition, large batch difference, and bring the risk of virus contamina-
tion (Fang et al., 2017; Gstraunthaler et al., 2013; Wessman and Lev-
ings, 1999). Besides, some components such as albumin, transferrin and
matrigel are also directly extracted from animals and therefore not sus-
tainable. To in accord with the purpose of cultured meat which is avoid-
ance of animal raising and slaughtering, all animal components should
be excluded in its production process. Furthermore, the development
of serum-free and animal component-free medium is fundamental to
3
Future Foods 3 (2021) 100032
ensure maximum safety, sustainability, controllability and accuracy of
cell culture process.
To date, some serum-free additives and medium are commercially
available, such as the B27TM (Thermo Scientific) and XerumFreeTM
(TNC Bio) additives and Essential 8TM (Life technologies) and
mTeSR1TM (Stemcell Technologies) medium. They have been demon-
strated to work well to support the ex vivo growth and stemness mainte-
nance of various cell types such as neural stem cells, hematopoietic stem
cells, mesenchymal stem cells (Hoang et al., 2020; Solis-Castro et al.,
2020; Wilkinson et al., 2019). Florini and Roberts (1979) tested a serial
of hormones, glycoproteins, and growth factors and showed that the pro-
liferation effect of myoblasts in F12 basal medium supplemented with fe-
tal globulin, insulin, and dexamethasone is comparable to the 10% horse
serum medium, but fetal globulin still derives from the FBS. The research
group of Dr. Post compared the effects of 3 commercial serum-free me-
dia with addition of 2 serum-replacements and several growth factors
on stimulating the cell proliferation of bovine myoblasts, and achieved
exponential cell expansion during 6 days of culture, albeit not to the
extent of serum-containing medium (Kolkmann et al., 2020). To date,
several cultured meat companies have publicly stated that they have
achieved the removal of animal serum in the production process, but no
further details were disclosed (Fusaro, 2021; Lucas, 2020; Mosa, 2019).
Because FBS is drawn from the fetus in pregnant cows during slaugh-
ter, containing hundreds of proteins and thousands of small molecule
compounds, simulation of the entire components in FBS is extremely
difficult and high cost (Bettger and McKeehan, 1986). It is practical and
feasible to develop serum-free medium aiming to one certain cell type,
achieving the precise nutrition supply in its proliferation and differenti-
ation process. Benefit from a plenty of studies on the mechanism of mus-
cle development in terms of the cell characteristics, signaling pathways,
gene and protein expression, high-throughput screening of compounds
X. Guan, Q. Lei, Q. Yan et al.
based on key pathways or targets will be one of effective approaches to
develop cell-specific animal component-free medium (Bentzinger et al.,
2012; de Freitas Almeida et al., 2016; Tu et al., 2016).
4.2. Intelligent bioreactor for scale-up
Design and development of intelligent bioreactors for cultured meat
is undoubtedly a technical challenge, whose expected scale would be the
largest ever in the mammalian cell culture field. Taking the production
of one ton cultured meat as an example, the desired cell number is in
the order of 1014 and the maximum accessible cell density in bioreactors
is 1~3 × 107 /mL, so one 10 m3 or ten 1 m3 bioreactors are the basic
configuration (Post et al., 2020). In vivo, the growth and development
of cells are inseparable from the interaction environment of various or-
gans, and likewise, the bioreactor should provide similar environment
for the cell ex vivo growth. In specific, it is necessary to artificially con-
struct the "heart" (mixing of nutrients), "lungs" (exchange of gases), and
"kidneys" (discharge of metabolic wastes) in bioreactors. If the overall
4
Future Foods 3 (2021) 100032
Fig. 2. Capital investment of cultured meat indus-
try. A) Total capital invested in cultured meat com-
panies over the years. B) Top ten companies regard-
ing the capital investment. Funding data are col-
lected from publicly available resources by Decem-
ber 31, 2020, not including companies that dedi-
cate cultured meat as part of business.
environment or local environment in the bioreactor is inappropriate, it
may cause precocious cell differentiation or apoptosis.
Various bioreactors can be applied for large-scale cultured meat
production and plenty of examples can be taken from the bioprocess-
ing of microbial fermentation and genetic engineering pharmaceutical
(Moritz et al., 2015; Stephenson and Grayson, 2018; Xing et al., 2009).
As a classic bioreactor, the stirred tank reactor has been successfully ap-
plied for the culture of different types of stem cells, such as mesenchymal
stem cells (Grein et al., 2016), embryonic stem cells (Borys et al., 2020)
and pluripotent stem cells (Manstein et al., 2019). However, for large-
volume stirred tank reactor the stirring intensity would be very high to
ensure the environment uniformity of the whole container, which might
generate shear stress that exceed the endurance capacity of cells and
lead to cell apoptosis (Allan et al., 2019). In contrast, bubble columns
such as air-lift reactors have no stirring parts, and the driving force of liq-
uid flow and mixing is the gravitational force acting on the entire reac-
tor volume, achieving lower and more uniform shear stress distribution
(Nienow, 2015; Zhang et al., 2020). Li et al. (2020) designed a 300 m3
X. Guan, Q. Lei, Q. Yan et al.
Fig. 3. Primary product interest of cultured meat companies.
air-lift reactor and estimated the optimal mass transfer, mixing and en-
ergy dissipation rate with computational fluid dynamics for cultured
meat production. Another popular bioreactor in the field of mammalian
cell bio-manufacture is the perfusion reactor, which has the advantages
in the flowing provision of nutriments and ejectment of metabolites.
Cimetta et al. (2007) designed and developed a perfusion bioreactor
with collagen sponges as the scaffold for the long-term culture of my-
oblasts and achieved improved cell viability, higher cell density, and
uniform cell distribution throughout the entire 3D scaffold. However,
it should be noted that different from the bioreactor designed for pro-
tein or compound production, the final product of cultured meat is the
muscle tissue cell itself, so the maintenance of morphology, character-
istic, and function of cultured cells in the bioreactor become extremely
important.
Except for the large scale, real-time monitoring, high cell densities
and low cost are expected to be achievable by bioreactors (Rafiq et al.,
2013; Simaria et al., 2014). Cultivation of cells on micro-carriers is
generally applied to achieve high density suspension culture of adher-
ent cells. Micro-carriers are beads to which cells can adhere and grow
in apposition. Because the bead surface is limited, new beads can be
added into the medium for bead-to-bead transfer of cells, achieving
the scale-up of production (Bodiou et al., 2020). Although the pro-
liferation and differentiation of myoblast, mesenchymal and pluripo-
tent stem cells have been reported on micro-carriers, harvest of cells
from micro-carriers is a key procedure that should be designed carefully
(Bodiou et al., 2020). In addition, the coating, surface modification, and
size of micro-carriers should be tailored according to cell and bioreactor
types (Moritz et al., 2015). Furthermore, medium recycling techniques
can be applied to achieve the maximum use of medium (Arshad et al.,
2017; Post et al., 2020). In specific, medium recycling is re-use of dis-
5
Future Foods 3 (2021) 100032
carded culture medium after removing toxic components and supple-
menting nutrient ingredients (Taya and Kino-Oka, 2011). Therefore, it
is necessary to monitor the change of main components in the medium
and make timely adjustments of medium components, which depends on
reliable process analysis technology. Apart from conventional monitor-
ing indicators including dissolved O2 and CO2 , temperature, pH, glucose
and lactic acid concentrations, cell-based indicators such as cell density,
morphology, characterized gene and protein expression is indispensable
(Xu et al., 2018). The location of sensor is worth to well considered to
ensure the accuracy and uniformity of collected data.
4.3. Degradable/edible scaffold for a 3D structure
The goal of cultured meat is to manufacture a piece of meat that
highly resembles the nutrition, appearance, texture and flavor of real
muscle tissue. However, conventional cell culture methods can only
achieve a plane thin layer of cells, which is almost invisible (Post, 2014).
The scaffold originated in the field of medical tissue engineering, which
are applied to provide an optimum microenvironment for tissue growth
and regeneration (Ferreira et al., 2020; Handral et al., 2020; Jiao et al.,
2020). In general, a scaffold is a 3D porous network that mimics the
structure and function of extracellular matrix, on which cells adhere,
grow, and perform a function. The porous structure allows the input of
gases and nutritive materials and output of metabolic waste, promot-
ing the maintenance of cell metabolism (Beale, 2014). Ideal scaffolds
should have a relatively large specific surface area for cell adhesion and
growth, flexible contraction and relaxation property, and good cell affin-
ity and cell compatibility. At the same time, its digestibility, edibility,
safety, economy, and scalability should be considered specially for cul-
tured meat (Browe and Freeman, 2019).
X. Guan, Q. Lei, Q. Yan et al. Future Foods 3 (2021) 100032

Fig. 4. Main production process of cultured meat. A muscle biopsy is performed on a living animal. Seed cells are isolated from a live animal biopsy and then
subjected to proliferation and myogenic or adipogenic differentiation. Cultured meat can be produced after food processing with ex vivo formed myofibers and
adipocytes.

Regarding the bio-based source of scaffold materials, usually they
can be divided into three categories based on degradability and ed-
ibility: non-edible, non-edible but degradable, and edible scaffolds
(Bodiou et al., 2020). As the constructing support for myofibers and
adipocytes of cultured meat, degradable or edible scaffolds are pre-
ferred. Synthetic polymers, such as poly (lactic-co-glycolic acid) (PLGA)
and polylactide (PLA), are popular degradable scaffold materials in the
field of tissue engineering (Liang et al., 2018; Patel et al., 2019). The
degradation products of these polymers are lactic acid and/or glycolic
acid, which are safe in food. If degradable scaffolds are used, they should
remain stable during the cell growth procedure and be degraded spon-
taneously or artificially before the acquisition of cultured meat prod-
ucts, so the degradation method and time should be well controlled to
prevent any cell damage or interferon of gene and protein expression.
Moreover, the residual amount of degradable material in the final prod-
uct should be detected although it might be considered as an ingredient.
In addition, physical methods or nontoxic reagents are preferred when
stabilizing the 3D scaffolds with desired high porosity and excellent hy-
drophilic performance (Sadeghi et al., 2016).
Alternatively, edible scaffolds that can be embedded in final cultured
meat products are another good choice. Native extracellular matrices in-
cluding collagen, gelatin, fibrin, etc., have a unique advantage as scaf-
folds due to their nature characteristics for cell attachment and growth
(Ali and Ahmed, 2018). MacQueen et al. (2019) developed a scaffold by
extruding gelatin microfibers and demonstrated that it supports the ad-
hesion, expansion, and maturation of muscle cells from cow and rabbit.
However, these native scaffolds are animal derived components, so the
use of them will fail to follow the fundamental goals of cultured meat.
Recently, recombinant expression of collagen or polypeptides has been
achieved by utilizing synthetic biology technology, showing promising
application to cultured meat (Fertala, 2020). In addition, natural mate-
rials such as alginate and chitosan are also edible biomaterials and have
been reported to support the 3D culture of myoblasts and adipocytes
(Ahmadi et al., 2015; Bodiou et al., 2020). As a part of the cultured
meat products, the texture, taste, thermal stability, cooking attribute
and nutritional value of scaffolds are required for evaluated, as well
as the economic and available for scalable production. Recently, a re-
search group in Israel has reported the use of textured soy protein as
a scaffold to create a 3D cultured meat product with bovine satellite
cells, smooth muscle cells and endothelial cells, achieving meaty fla-
vor and sensorial attributes after cooking. Unfortunately, they provide
no information about the nutrition or the actual advantage on the final
product quality properties by having endothelial cells (Ben-Arye et al.,
2020).
4.4. Reduced cost for culture medium ingredients
Recently, cultured chicken, beef, and seafood products have been
manufactured by some research groups on a pilot or larger scale, with an
announced cost ranged from $66.4/kg to $2200.5/kg (Scipioni, 2020;
Starostinetskaya, 2021). In contrast, the retail price of conventional
meat is $2.1–3.9/kg for broiler chicken, $5.6–10.2/kg for beef cat-
tle, and $2.7–7.1/kg for pork, far less expensive than current cultured
meat cost (USDA, 2021). Therefore, cost reduction remains a high pri-
ority in the development and optimization of cultured meat produc-
tion process. Throughout the production process of cultured meat, the
most significant cost driver can be attributed to the culture medium,
which contributes 55% to 95% of the production cost (Kolkmann et al.,
2020).
In serum-free medium, cytokines are the most important components
that support the cell growth and regulate the cell behavior, as well as
the most expensive components. For example, the cost compositions of
Essential 8TM and DMEM with an addition of G-5 SupplementTM are
showed in Fig. 5. Essential 8TM is a commercial serum-free medium that

6
X. Guan, Q. Lei, Q. Yan et al.
Fig. 5. Cost compositions of Essential 8TM and DMEM with an addition of G-5 SupplementTM . A) Essential 8TM medium. B) DMEM with an addition of G-5
SupplementTM .
has been used frequently for cultivation of various cell types from sev-
eral different species (Naung et al., 2019; Xiao et al., 2018). G-5 Sup-
plement is a chemically defined serum-free supplement that includes 2
kinds of cytokines bFGF and EGF which are proved to significantly pro-
mote the proliferation of muscle stem cells (de Freitas Almeida et al.,
2016; Wei et al., 2011). It is obvious that in Essential 8TM 96% of the
cost is attributed to cytokines and in DMEM with G-5 SupplementTM
88% of the cost is Transferrin and cytokines, all of which are proteins.
Therefore, bringing down the cost of added proteins is the most critical
step in reducing the total medium costs.
The high price of cytokines is not due to the technical difficulty
in production, but their scientific research or medical attribute, which
possesses relatively low industrial scale but the highest industry stan-
dards, including the purity, impurity component, endotoxin, and so on
(Choudhury et al., 2020). The production cost of many industrial-scale
enzymes that are consumed in large quantities in the processing of food
and daily necessities like lipase, cellulase, and amylase are nearly $4
per gram, more than 104 -fold lower than the production cost of cy-
tokines (evaluated according to the retail price deducting 80% of profits)
(Specht, 2020). Therefore, it may be useful to develop the food-grade
standard of cultured meat ingredients, so that low-cost cytokines are
available on the market. Moreover, it is often said in the fermentation
industry that greater scale creates lower cost per unit of output, so the
cytokine price inevitably decreases with the intensity of profession com-
petition and expansion of production scales.
Another way to reduce costs is by using protein hydrolysates that
derived from plants or microorganisms as basic medium ingredients or
even serum supplements. Protein hydrolysates are products obtained
after enzymatic, acid or alkali hydrolysis of proteins, and their main
components are peptides, with small amounts of amino acids, sug-
ars, lipids, minerals, and vitamins (Pasupuleti and Demain, 2010).
Plenty of functional hydrolysates have been identified and applied to
culture various animal cell types (Kim and Lee, 2009; Slivac et al.,
2018; Taghizadeh et al., 2020). Jo et al. (2020) investigated and
found that whey protein hydrolysates prepared using Protamex and
Alcalase can promote the proliferation and differentiation of MC3T3-
E1 osteoblasts. Hu et al. (2017) reported that yeast extracts can con-
tribute to cell growth and antibody production of CHO cells. Okamoto
7
Future Foods 3 (2021) 100032
et al. (2019) proved that the use of algal extracts as a substitute for
glucose and amino acids of basal culture media to support the growth
of C2C12 mouse myoblasts. Although protein hydrolysates are widely
available, cheap, and have shown some benefit effects on cell growth,
their mechanism is not totally definite. Moreover, variable raw material
sources and not completely clear components might lead to great differ-
ences between batches of products (Lobo-Alfonso et al., 2008). There-
fore, future studies should focus on muscle-related cell types to investi-
gate the function and mechanism of protein hydrolysates in more depth
and improve their production process, quality control, and evaluation
system accordingly.
5. Regulatory and social challenges for cultured meat
5.1. Safety evaluation and regulatory policy
As a kind of brand new meat products, the safety evaluation and reg-
ulatory policy of cultured meat need to be studied and formulated cau-
tiously. Regarding the regulatory status of global cultured meat industry,
the European Union (EU) was the first initiator, the United States was
the most active promoter, and Israel and Singapore were positive partic-
ipants (Listek, 2020; Post et al., 2020). In EU, the EU Novel Foods Reg-
ulation [(EU) 2015/2283], which came into force on 1 January 2018,
explicitly lists products produced through animal cell or tissue culture as
new foods, clearing the legal hurdles for the marketing of cultured meat
(EFSA, 2018). In United States, the Food and Drug Administration (FDA)
and the US Department of Agriculture Food Safety and Inspection Ser-
vice (USDA–FSIS) have introduced a joint regulation frame to regulate
cultured meat after several discussions (FDA, 2019). In Australia, Food
Standards Australia New Zealand (FSANZ) which is a statutory author-
ity to develop food standards for Australia and New Zealand announced
that cultured meat could be included in their existing Food Standards
Code but specialized premarket approval is needed (FSANZ, 2017). In
China, the supervision system and relevant regulations are being set up
and improved for the cultured meat industry. Chinese researchers sug-
gested that cultured meat should be regarded as a new food raw material
and managed according to the National Management Method for Safety
Review of New Food Raw Materials (Wang et al., 2019). The security
X. Guan, Q. Lei, Q. Yan et al.
of donor animals and the whole process of cultured meat production
should be supervised strengthen, and an independent standard system
and an objective regulatory system should be developed to assess the
food safety risk and nutrient composition. Just in December 2020, Sin-
gapore regulators claimed to approve the application of publicly sell of a
cultured chicken product by the company called Eat Just, becoming the
world’s first regulatory issued for cultured meat (Poinski, 2020). How-
ever, no specific information about the texture, flavor, and nutrients
including the amino acid composition, protein, fat, and mineral content
of this product can be searched.
The food safety risk of cultured meat involves in the chemical
safety, bio-safety, and nutrition security during the production process
(Wang et al., 2019). The medium components and extra additives for
cell proliferation and differentiation, the materials of scaffolds, and the
use of antibiotics and hormones should be in accord with relevant reg-
ulations (Chriki and Hocquette, 2020; Fujita et al., 2010; Lowe, 2006;
Schnitzler et al., 2016). It is worth noting that for some additives it is
necessary to develop usage specification regarding food products due to
their first application in food area. In terms of the bio-safety of cultured
meat, the potential variation of genes and proteins of cells due to long-
term cultivation in vitro should be evaluated before premarket approval.
If gene modification is applied during the production process, sensitiza-
tion, toxicity and tumorigenicity evaluation of the whole product should
be executed in strict rotation (Edelman et al., 2005; Mohorcich and
Reese, 2019). In a word, the evaluation criteria of food safety and policy
regulation aiming at all materials and products in the industrial chain
of cultured meat need to be introduced as early as possible, which can
provide guidance to cultured meat research.
5.2. Public perception and acceptance
Issues of public perception and acceptance are always challenges in
emerging technologies and products, and cultured meat is no exception
(Bryant, 2020). Bryant and Barnett (2018) performed a systematic re-
view based on 14 studies about the consumer acceptance of cultured
meat and found conflicting responses in trying cultured meat. Cultured
meat is more acceptable to people who are familiar with it or after
being informed of the benefits of cultured meat for environment and
healthy. The consumer concerns focus on the uncertain food safety and
price, such as unnaturalness, unhealthy, not tasty, and unexpected price.
Rolland et al. (2020) investigated the customer acceptance of cultured
meat after tasting and emphasized the effect of positive information in
improving acceptance and willingness to taste cultured meat. Surpris-
ingly, 58% of the respondents were willing to pay a premium for cul-
tured meat of, on average, 37% above the price of regular meat.
Although cultured meat is generally targeted at meat eater, it may
attract some vegetarian-leaning individuals who don‘t eat meat due to
compassion for animals, so the potential environmental and animal wel-
fare benefits of cultured meat should be fairly estimated and propagan-
dized (Siegrist et al., 2018). A summary on cultured meat-related online
news comments in United States reveals more critical responses about
cultured meat such as “unnatural” and “unappealing” (Laestadius and
Caldwell, 2015). Therefore, except for striving to make technological
breakthrough, the public science popularization about cultured meat
should be carried out through multiple channels. The development pur-
pose, production technology, advantage and disadvantage of cultured
meat, as well as the nutrition value, food safety and health effect of
products, should be popularized to the public without bias. Once con-
sumers establish correct perception, they can choose whether to eat and
when to eat cultured meat.
6. Conclusion
As a novel food production technology, cultured meat might revolu-
tionize meat supply by a more efficient, green, and sustainable way. A
8
Future Foods 3 (2021) 100032
lot of capital investment and strong business competition will undoubt-
edly facilitate the research process and shorten the timeline for the com-
mercialization of cultured meat. Advanced technologies could speed up
the development and optimization of animal component-free medium,
high-volume bioreactor, and edible scaffolds, and the production cost
might be reduced significantly soon. However, there are fundamental
issues in terms of nutritive value, texture and flavor that need to be
investigated deeply. More importantly, regulatory policy on the whole
process of production including plant construction, raw material pur-
chasing, manufacturing process, quality control of seed cells and final
products should be formulated. Especially whether gene-editing, gene
transfection or even transgenic technologies can be applied to cultured
meat deserves to be widely discussed. Furthermore, media and corpo-
rate publicity for the sustainability, food safety, nutrition and health of
cultured meat should be neutral and accurate. In general, with increas-
ing demand of meat consumption and rapid development of cultured
meat industry, cultured meat will capture loyal consumers and possess
significant market shares in the near future.
Acknowledgements
The authors acknowledge the Good Food Institute for providing cul-
tured meat company and product information.
Financial Support
This work was supported by the Natural Science Foundation of
Jiangsu Province (BK20202002), and the Consulting Project of the Chi-
nese Academy of Engineering (2020-XY-1722).
Declaration of Competing interest
None.
Author Contributions
Xin Guan drafted the manuscript, Qingzi Lei and Qiyang Yan col-
lected the data with input and supervision of Xueliang Li, Jingwen Zhou,
Guocheng Du and Jian Chen. All authors provided critical feedback and
contributed to the final version of this manuscript.
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