Cultivated
Cost-effective media development and optimisation for cultivated meat and seafood applications
Very few cell culture media formulations (including growth, maintenance, or differentiation growth factor cocktails) are publicly available for animal species and cell types relevant to cultivated meat.
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Cultivated
- Media optimisation
Resources
- Deep dive: Cultivated meat cell culture media
- Cost drivers of cultivated meat production seminar and slide deck
- Analysing cell culture medium costs – a whitepaper by GFI
- Cultivating alternative proteins from commodity crop sidestreams
- Applications and analysis of hydrolysates in animal cell culture
B8, a further-optimised version of Essential 8 media at a fraction of the cost (also commercialised).
Current challenges
Very few cell culture media formulations (including growth, maintenance, or differentiation growth factor cocktails) are publicly available for animal species and cell types relevant to cultivated meat. Any existing formulations have typically been optimised using high-value R&D inputs rather than for cultivated meat-relevant considerations of cost or performance. Key findings from GFI’s Techno-Economic analysis for the production of cultivated meat indicated that recombinant proteins (such as albumin and transferrin) and growth factors in the cell culture medium are the dominant cost drivers of the end product. Therefore, cost reductions in growth factors and recombinant proteins hold the largest opportunity to reduce COGS in the industry. It is also necessary to reduce duplicative efforts and cost of innovation by enabling open access sharing of optimised formulations that enable researchers and industry to take a faster path to commercialisation.
Proposed solutions
- Systematic optimization using approaches such as Design of Experiments (DOE) or other more sophisticated algorithms should be applied to identify serum-free media formulations for maintaining cell types at the desired transcriptional state (for example, stemness or higher proliferation rate).
- Systematic investigation of growth factor needs and effects for achieving various cell states for cultivated meat development
- Mapping animal cell metabolism and secretome to optimise media formulation
- To understand a cell’s metabolism, a genome-scale metabolic model (GEM) can be created to map cell metabolism, including the flux of metabolites and bottlenecks in metabolic pathways. Some organisms already have draft GEMs, but they require additional experimental validation (e.g., salmon, bovine, shrimp, chicken). Other GEMs have already been validated in many experimental settings, making them more robust (e.g., CHO cells, zebrafish). These existing GEMs can inform the creation of new GEMs, especially when organisms are closely related at the evolutionary level and share metabolic pathways and enzymes. Such robust GEMs can be adopted by researchers in academia and industry to formulate and optimise tailored media for cultivated meat production.
- In high-density bioprocesses, signalling factors secreted by stem cells can accumulate to high concentrations and dramatically influence the behaviour of neighbouring cells (through paracrine signalling effect). A better understanding of which factors influence proliferation, differentiation, and other cellular traits is needed and can be achieved by mapping the secretomes of cultivated meat-relevant cell types. The secretomes from a variety of human stem cell populations have been analysed previously, providing protocols for collecting secreted factors and characterisation via mass spectrometry, gene chips, and sequencing analyses. Cultivated meat researchers can leverage these methods for collecting data on the secretomes of animal myoblasts, adipocytes, and other relevant cells, informing future bioprocessing strategies and media optimisation efforts.
- Rather than relying on purified recombinant growth factors, exploratory research into the use of conditioned media from animal cells that produce high levels of function-specific molecules compatible with cultivated meat cells’ needs and contain few or no undesirable cellular waste products could be explored.
- Identifying and validating low-cost functional substitutes (non-recombinant) for serum in animal cell culture with suitable functionality to mimic the roles of serum albumin and transferrin and allow for greater scalability (e.g., higher-performing plant protein hydrolysate ingredients via direct extraction from agri-waste or algal ‘serum’ proteins are scalable alternatives). The viability of incorporating non-conventional media components into culture media while still meeting the performance requirements of the cells would require focused research into various hydrolysate processing stages, such as:
- Raw material selection offers the best cell culture media nutrition, performance, cost, sustainability, and consistency.
- Hydrolysis protocol optimisation for highest nutrient availability and minimal undesirable anti-nutritional or growth inhibitory factors.
- Filtration & purification methods with consistent QA/QC and minimal batch-to-bath variability.
- End-product characterisation by testing the performance of the various hydrolysates in cells relevant to cultivated meat manufacturing.