Compared to sourcing plant bioactive molecules through traditional harvesting, PCC provides a highly controlled, year-round production platform largely unaffected by geography and climate. Beyond these advantages, this approach also offers improved sustainability, consistent product quality, and enhanced metabolite yields.

Bypassing Conventional Constraints

One of the primary drivers for adopting PCC is the capacity to overcome limitations inherent to traditional agriculture, including geographical dependence, seasonal variations, and vulnerability to climatic or pest-related disturbances (5). Under in vitro conditions, plant cells can be grown throughout the year in highly controlled environments, ensuring a reliable supply of valuable secondary metabolites (6). In addition to temporal flexibility, PCC systems bypass arable land requirements. This is particularly relevant for species that thrive in narrow ecological niches; cells sourced from endangered or geographically restricted plants can be multiplied in flasks or bioreactors without further straining wild populations (7). For example, approximately 3 kg of dry bark from a slow growing yew (Taxus sp.) tree is required to supply a single dose (300 mg) of paclitaxel (8, 9). Alternatively, PCC based on Taxus chinensis cell is used by Phyton Biotech® to produce 100 kg of paclitaxel per year, with 20% of cost of goods compare to natural harvest (10).

Sustainable and Eco-Friendly Production

The ecological footprint of PCC is often lower than that of conventional cultivation, as it dispenses with large tracts of farmland and removes the need for pesticides. Additionally, harvesting chemicals from tree bark or heart wood requires an immense amount of energy and generates a high amount of global warming potential (GWP) (11). Indeed, a recent study suggested that compared to natural harvest, PCC based natural product production lead to 23% reduction in GWP (12), largely due to the drastic reduction (94.3%) of energy requirement during extraction stage. Another study has highlighted (13) electricity as a dominant factor in PCC’s environmental footprint, which can be reduced through optimisation bioreactor condition, including improvements in mixing efficiency, cultivation time, and the adoption of renewable energy sources including wind or photovoltaic systems.

Consistency and Quality Control

Because PCC is carried out in aseptic, closed environments, operators can enforce stringent sterility measures and standardised media formulations. It has been reported that tissue-cultured ginseng (Panax ginseng C.A. Meyer) is stable in quality, and is more effective at promoting gastrointestinal propulsion in animal models compared to filed cultivated ginseng with no mutagenic potential (14). Additionally, production costs of cultivated ginseng were comparable to field-cultivated ginseng, making the product commercially viable for health food markets. Another milestone that demonstrates PCC’s quality is the Food and Drug Administration’s (FDA) approval of plant cell-based paclitaxel in 2000 (15).

Potential for secondary metabolism yield enhancement

Another advantage of PCC is application of stimuli to enhance its secondary metabolite yield. Stimuli can be chemical, like elicitors and precursors feeding; or non-chemical, like mechanical force, light and temperature (16-18). For example, application of Botrytis cinerea homogenate, a fungal lysate, has been reported to enhance sanguinarine yield by 18 folds in Papaver somniferum cell culture (19). In Vitis vinifera suspension culture, addition of phenylalanine and methyl jasmonate combination, led to a 4.6-fold increase in anthocyanin content compared to control (20). Metabolic engineering has been explored in PCC to enhance secondary metabolite production and direct metabolism flow. It has been demonstrated that overexpression of Coptis (S)-scoulerine 9-O-methytransferase (SMT) in Coptis japonica cell led to approximately 15% increased accumulation in berberine and columbamine, and ectopic expression of SMT in Eschscholzia californica cultured cell led to production of columbamine in resulting cell line, which was not presence in non-transgenic cell (21).

PCC systems leverage diverse techniques to optimise the production of cosmetic actives. These methods, rooted in plant cell totipotency, enable scalable and controlled biosynthesis of secondary metabolites. Below, we outline key methodologies and their relevance to industrial applications, including callus induction, suspension culture and cell line selection.

Callus Culture and Maintenance

Callus formation serves as the foundation for most PCC workflows. Explants (e.g., leaf, stem, or root segments) are sterilised and cultured on solid media supplemented with auxins and cytokinins to induce dedifferentiation (22). Regular subculturing is performed to mitigate the genetic instability and maintain metabolic productivity (23). In practice, identifying optimum media and conditions to support plant cell growth and metabolite production can be difficult and often require full or fractional factorial screen (24).

Despite the difficulties, callus cultures have been demonstrated to produce secondary metabolites. These include phenolic (25), flavonoids (26), alkaloids (27) and terpenoid (28). Although plant cells are considered to be totipotent, callus can be induced from any plant tissue under the optimum callus induction condition through dedifferentiation process. Undifferentiated tissue, like meristematic cambium, has been used as an explant to initiate plant cell culture. This offers advantages compared to traditional dedifferentiated cells, including resistance to shear stress and secondary metabolite production (29).

Suspension Culture Systems

Suspension culture is the most practical approach to industrial-scale metabolite production (30) where friable callus is transferred into agitated liquid media under carefully defined parameters such as temperature, aeration and agitation (31). This environment facilitates uniform nutrient uptake, promotes consistent cell division, and can enhance secondary metabolite synthesis upon elicitation or induction. For instance, silver nanoparticle elicitation led to 9.54 mg/g dry weight (DW) of cichoric acid yield from Echinacea purpurea suspension culture (32). PCC in suspension can be upscaled for large-scale secondary metabolites production (33), with tailored bioreactor design to accommodate plant cell features such as slower growth and susceptibility to shear force. Successful examples include production of anthocyanins using Vitis vinitera suspension culture in stirred fermenter (34); and production of rosmarinic acid with Satureja khuzistanica suspension culture using a wave-mixed bioreactor (35).

Strain Improvement

Strain improvement is the cornerstone of optimising PCC for industrial-scale production of cosmetic actives. This process involves selecting high-performing cell lines and refining their metabolic pathways to maximise yield, consistency, and scalability. Heterogeneous cell populations derived from callus or suspension cultures are screened to isolate clones with elevated biosynthetic capacity. For example, selection of Coptis japonica cell line has led to isolation of several C. japonica cell lines with average berberine production titre at 0.9 g/L and highest berberine production titre at 1.39 g/L, while the unselected cell line’s productivity was 0.23 – 0.30 g/L (36). Advanced techniques such as fluorescence-activated cell sorting (FACS) enable rapid identification of high-yielding cells using metabolite-specific probes. In Ophiorrhiza mungos, this approach, combined with jasmonic acid elicitation, elevated camptothecin yields to 1.12 mg/g DW, compared to 0.06 mg/g DW in unoptimised lines (37).

Metabolic engineering leverages genetic tools like CRISPR-Cas9 to edit biosynthetic pathways precisely. The overexpression of rosmarinic acid synthase (RAS) in Coleus blumei hairy root cultures elevated rosmarinic acid accumulation by 40% compared to wild-type lines, enhancing antioxidant capacity for anti-aging formulations (38). Concurrently, heterologous expression of Hyoscyamus muticus hyoscyamine 6β-hydroxylase (H6H) in Atropa belladonna hairy roots enabled de novo biosynthesis of scopolamine, a compound absent in untransformed cultures, achieving yields of 4.2 mg/g DW (39).

PCC-derived metabolites are revolutionising skincare formulations due to their targeted bioactivity, purity, and alignment with sustainable consumer preferences. Rosmarinic acid, produced in Salvia viridis hairy roots, scavenges 85% of free radicals at 0.1% concentration, offering potent UV protection (40). Centella asiatica callus cultures yield madecassoside (1.3% - 2.8% DW) and asiatic acid (0.15 – 0.25 % DW) (41), which enhance collagen synthesis in human dermal fibroblasts (42). Vitis vinifera suspensions elicited with pectin achieve anthocyanin titers of 4.2 mg/g DW (43), providing stable pigments for anti-aging serums. Withaferin A, known to reducing NF-κB-driven inflammation in animal model (44), has been reported to be produced by Withania somnifera hariy root cultures produces at titre of 218 µg/g DW (45). Leading brands like Mibelle Biochemistry (RootBioTec™ HW) and Unhwa Corp. commercialise PCC extracts as “plant stem cells,” capitalising on their rejuvenating effects. These products align with the $8.7 billion 2023 ‘clean beauty’ market, which is projected to grow at 16.65% CAGR through to 2033 (46).

The convergence of biotechnology and computational tools is poised to unlock unprecedented precision and sustainability in PCC systems (47). Notably, overexpressing the Hyoscyamine 6β-Hydroxylase(H6H) gene in Scopolia parviflora hairy roots can elevate scopolamine production up to ~8 mg/g DW, three times more than wild-type root (48). Furthermore, CRISPR-Cas9 and base-editing technologies have demonstrated targeted pathway optimization in medicinal plants (49), for instance, knock-out H6H in Atropa belladonna result in diminished anisodamine and scopolamine production and higher hyosyamine production (50).

Synthetic biology platforms, including yeast-based prototyping of plant pathways, also accelerate strain development. For instance, high-titer production of artemisinic acid (25 g/L) in engineered Saccharomyces cerevisiae (51) guided subsequent improvements in Artemisia annua cultures. In parallel, machine learning models trained on multi-omics data increasingly predict optimal elicitor combinations and culture conditions with high accuracy, leading to gains in secondary metabolite yield (52). A recent study in Corylus avellana cell culture used general regression neural network (GRNN) and fly optimisation algorithm (FOA) to optimise elicitation regime and lead to improved paclitaxel yield (53).

On the bioprocess side, digital twin simulations help reduce scale-up risks and streamline process development (54), while closed-loop bioreactors with integrated nutrient recycling can significantly cut water usage (55). Solar-powered photo-bioreactors, often employed in microalgae systems, are now being considered for plant cell cultures, potentially lowering operational energy costs. Lastly, single-cell RNA sequencing (scRNA-seq) is emerging as a powerful tool to pinpoint and selectively propagate high-producing cellular subpopulations (56). Studies in Taxus mairei, for example, revealed cell specific for taxol biosynthesis, providing new knowledge for bioengineering taxol production (57).

PCC stands at the forefront of sustainable innovation in the cosmetics industry, offering an ecologically responsible alternative to conventional raw-material sourcing. Through precise control of growth conditions, PCC mitigates the risks posed by climatic fluctuations, over-harvesting, and ethical dilemmas tied to endangered species. In addition, the method significantly lowers global warming potential compared to wild-harvested plants, advancing the clean beauty movement.

Looking ahead, several key developments are poised to accelerate PCC adoption. First, AI-driven fermentation and bioprocessing optimisation will refine scale-up protocols and reduce production costs, thereby encouraging wider industrial uptake. Second, data- and modelling-driven gene editing will enable fine-tuned modifications that optimise secondary metabolite pathways for greater yields and tailored bioactivity. The regulatory precedent set by plant cell-derived pharmaceuticals (e.g., paclitaxel) can guide the harmonisation of global safety standards for novel cosmetic ingredients, ensuring both efficacy and consumer confidence.

In tandem, education and transparency will remain pivotal. Public awareness of PCC’s non-GMO scope and smaller ecological footprint can foster trust and acceptance. Finally, cross-sector collaborations including biotechnologists, policymakers, and industry leaders will be critical for developing renewable energy-powered bioreactors and fully circular nutrient systems. These interdisciplinary efforts promise to solidify PCC’s position as not just an alternative, but a cornerstone for a greener, scientifically advanced future in the cosmetic industry.