Join us at Cultivate 2023 where our CEO, Dr Catherine Elton, will be giving a talk on “Growth factors for cellular agriculture: why we need to worry about species-specificity during media optimisation”. Read the full abstract below.
Cultivate is a multi-voiced forum intended to support informed dialogue about the emergent field of cellular agriculture from UK perspectives. Cultivate, established in 2016, was created to contribute to events, maintain an online presence, and provide a focal point for UK cellular agriculture activity.
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Growth factors for cellular agriculture: why we need to worry about species-specificity during media optimisation
Cellular agriculture has the potential to transform food production and impact the health and well-being of future generations. Immediate priorities for cultivated meat process development include cell culture media optimisation to support multiple cell expansion and maturation stages in bioreactor conditions and replace animal-derived components, such as foetal bovine serum (FBS). Growth factors are essential components of cell culture media and provide a carefully orchestrated set of biochemical signals to control cell growth and fate.
There is much emphasis on cost reduction of growth factors to facilitate scale-up. However, a dearth of research focuses on the impact of species specificity on efficacy and hence inefficiency in culture systems. This is partly due to the lack of availability of commercial reagents, poor annotation of relevant genome sequences and lack of comparative studies.
We have surveyed all growth factors used in cultivated meat processes and used bioinformatic and structural analysis to identify those that raise concerns over potential species-specific activity such as hepatocyte growth factors (HGF), epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Focusing initially on HGF, an important growth factor in bovine myoblast expansion media, we first produced an animal-free native sequence active isoform of human HGF, HGF NK1, as existing commercial proteins are primarily produced using animal or human cell protein expression systems. HGF NK1 efficacy was determined in well-characterised stem cell differentiation protocols to human hepatocytes. Building on this, we have produced equivalent bovine and porcine-specific proteins and determined biological activity in luciferase reporter assays. These proteins are currently being evaluated for cultivated meat media development.
Gaining an improved understanding of species specificity will allow targeted protein engineering techniques to be applied to achieve enhanced biological performance and growth factor manufacture yield to meet the ultimate price-point requirements of the industry.