plant cell technology

The production of drugs, cosmetics, and food that are derived from plant cell and tissue cultures has a long tradition. The emerging trend of manufacturing cosmetics and food products in a natural and sustainable manner has brought a new wave in plant cell culture technology over the past 10 years. More than 50 products based on extracts from plant cell cultures have made their way into the cosmetics industry during this time, whereby the majority is produced with plant cell suspension cultures.

In addition, the first plant cell culture-based food supplement ingredients, such as Echigena Plus and Toeside 10, are now produced at the production scale. In this mini-review, we discuss the reasons for and the characteristics as well as the challenges of plant cell culture-based productions for the cosmetics and food industries. It focuses on the current state of the art in this field. In addition, two examples of the latest developments in plant cell culture-based food production are presented, that is, a superfood that boosts health and food that can be produced in the lab or at home.

Introduction

In 1902, the Australian botanist Gottlieb Haberlandt provided the basis for the usage of plant cell and tissue cultures (Haberlandt 1902). He described the formation of callus (unorganized cell mass in response to wounding) from adult plant cells and its regeneration into a complete plant for the first time. This phenomenon, also known as cellular totipotency of plant cells, was experimentally demonstrated by growing carrot cells in vitro by Haberlandt in 1958 (Fehér 2015). Between the 1960s and the 1980s, many studies were executed in order to mass propagate plant cell cultures and to develop bioprocesses delivering secondary metabolites for the pharmaceutical, food, and cosmetics industries.

Different commercial secondary metabolites (e.g., shikonin, scopolamine, protuberances, rosmarinic acid, ginseng saponins, and immunostimulating polysaccharides), which are based on plant cell cultures, entered the market between the early 1980s and late 1990s (Sato and Yamada 1984; Deno et al. 1987; Ritterhaus et al. 1990; Hess 1992; Hibino and Ushiyama 1999). A further milestone in plant cell culture technology is represented by the FDA (Food and Drug Administration) approval of the anticancer compound paclitaxel in 2000.

Cells from the Pacific yew grown in 75 m3 stirred bioreactors to deliver up to 500 kg of this medicinally important secondary metabolite per year (Imseng et al. 2014; Steingroewer 2016). The advantages of the production of secondary metabolites with plant cell cultures over conventional agricultural production with whole plants are indisputable (Hussain et al. 2012). There is no seasonal dependence on in vitro production of secondary metabolites, and controlled manufacture via standardized batches is possible. Furthermore, the impact on the ecosystem is low, the water needed and carbon footprint are reduced, and pesticides, as well as herbicides, are not required. Nevertheless, the number of commercial production processes of secondary metabolites involving plant cell cultures is low. This particularly concerns pharmaceutical applications and is ascribed to somaclonal variations of the production clones as well as too low secondary metabolite titers (Sharma et al. 2014).

Product approval in the pharmaceutical industry differs from that in the cosmetics industry, where no official approval is required and where the manufacturing company is responsible for product safety (Zappelli et al. 2016). Moreover, innovations and developments in the cosmetics industry, which introduced hundreds of new cosmetics products every year, are strongly driven by the consumer. The consumer wants to have not only effective, safe, and natural but also sustainable, cosmetics products, whose manufacture does not negatively affect the environment (Schmidt 2012; Fonseca-Santos et al. 2015). In respect of the cosmetics industry, there is high interest in plant cell culture extracts with multiple specific activities for skincare, make-up, and hair care as supplement ingredients.

Plant cell culture extracts containing a mixture of bioactive ingredients (and not only secondary metabolites) can already be produced under controlled conditions. Moreover, even extracts from rare or endangered plant species can be made available by applying plant cell culture technology. It is also worth mentioning that plant cell culture extracts can be used in minimal concentrations in the final cosmetics formulations (Barbulova et al. 2014). In other words, a low product titer is less critical than in pharmaceutical applications, especially since the plant cell culture extract may act in a synergistic manner as described by Carola et al. (Carola et al. 2012). Consequently, the large number of cosmetics products that have been manufactured with plant cell culture technology over the past 10 years is hardly a surprise. Indeed, it explains the renaissance in plant cell culture technology that has taken place.

The developments in the cosmetics industry have influenced the food industry, where new manufacturing methods for food and food ingredients are also in demand. Various studies have reported that supplying the world population with both animal and plant-based food in sufficient quantity and quality will become increasingly difficult. For example, according to the estimates of Alexandratos and Bruinsma, 60% more food will be required by 2050 than is manufactured today (Alexandratos and Bruinsma 2012), and traditional farming will not be able to meet these requirements. Cellular agriculture is assumed to be one solution here (Foussat and Canteneur 2016; Mattick 2018; Nordlund et al. 2018). Plant cell-based cellular agriculture uses plant cell cultures to manufacture high-value food ingredients (Stafford 1991; Fu et al. 1999; Ravishankar et al. 2007; Nosov 2012; Davies and Deroles 2014).

Ginseng triterpene saponins manufactured with plant cell cultures in bioreactors have been used as food supplement ingredients for a considerable time (Wu and Zhong 1999; Sivakumar et al. 2005; Paek et al. 2009), but many plant cell culture lines producing food supplement ingredients have not reached commercial production. Due to the latest approaches to engineer homogeneous and high-productivity cell lines without genetic engineering (Yun et al. 2012; Sood 2017), plant cell culture technology for food products is regaining interest. Climate change and plant diseases reducing the production of plant-based food are driving this trend, and first scientific studies have suggested that plant cell cultures or their extracts may themselves be used as foodstuffs (Räty 2017; Nordlund et al. 2018).

This mini-review describes the current state of plant cell culture technology aimed at products for the cosmetics and food industries. Based on an overview of plant cell culture extracts which have been launched by European and US companies over the past 10 years, we present the main plant cell culture types of interest, their establishment, the mass propagation in bioreactors, and the related challenges. In addition, the production of plant cell culture extracts following the bioreactor cultivation step is briefly discussed.

Finally, two examples of the latest developments in plant cell culture-based food production are given. However, plant cell culture-based manufacture of recombinant proteins (Tschofen et al. 2016) is not covered, as the vast majority of cosmetics and food companies, particularly those located in Europe, do not use genetically modified plant cell and tissue cultures, which are the precondition for the production of recombinant proteins with plant cell culture technology.

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