Cell culture media for cultivated meat: Review and perspectives on first principles design to drive cost-effective scale-up

Background: Cultivated meat (CM) has the potential to complement conventional meat while reducing the environmental footprint of food production to meet the growing global protein demand. Cell culture medium is not only a critical production input but also a major cost-driver, estimated to contribute to 31–99 % of CM production costs at scale. Typical culture media optimized for biomedical applications are unsuitable for CM due to their high costs and their reliance on animal-derived components such as serum, which is poorly chemically-defined. Scope and approach: Here, we review recent advancements in culture media development for bovine, chicken, and porcine CM applications and propose a first principles approach for cost-effective CM media development. Key findings and conclusions: The majority of efforts to reduce media costs by eliminating serum, optimizing growth factors, and replacing animal-derived components with alternatives including from recombinant sources have fallen short of achieving stable long term cultures with optimal cell proliferation and differentiation rates to achieve high quality CM biomass. Our current understanding of the roles of key media components such as glucose, lipids, growth factors, and hormones is limited, which is prolonging much needed cost-effective innovations in CM media. We propose investigating and prioritizing essential components for CM-specific cell physiology and metabolism while eliminating unnecessary additives, then employing technoeconomic analysis for further optimization towards scale-up production. This targeted approach can help create cost-effective serum- or animal-free culture medium solutions to enable scalable CM production and help accelerate adoption of CM as a sustainable protein source.