Researchers from The Cultivated B and various academic institutions have identified a novel guanylhydrazone-based small molecule, TCB-32, that could serve as a synthetic alternative to basic fibroblast growth factor (bFGF) in cell culture applications.

This discovery holds potential implications for the scalability, consistency and cost-effectiveness of cell-based products, including cultivated meat and cell therapies.

bFGF is a critical component in cell culture media, facilitating cell proliferation and differentiation. However, its use presents challenges related to variability, sourcing and cost.

The introduction of a synthetic replacement could alleviate these issues, enhancing the reproducibility of cell culture processes essential for large-scale production.

The research team, led by Mikhail Feofanov and a consortium of scientists including Gerrit Martin Daubner, Andrea Saltalamacchia and others, used structure-based virtual screening to identify TCB-32 as an FGFR1 agonist.

This molecule mimics the action of bFGF, activating the FGFR1 signaling pathway to promote cell proliferation. Notably, TCB-32 demonstrated enhanced thermal stability, maintaining its activity over several days, a significant improvement over bFGF.

Through extensive structure-activity relationship studies, the team was able to refine TCB-32, leading to the development of three highly potent agonists: TCB-494, TCB-541, and TCB-621. These compounds exhibited decreased effective concentration (EC50) values, indicating increased potency and efficacy in stimulating cell growth.

The findings suggest that these synthetic molecules could effectively replace bFGF in serum-free media, potentially addressing bottlenecks in large-scale cell production.

The ability to maintain consistent cell growth without reliance on animal-derived growth factors aligns with the industry's shift towards more sustainable and ethical production methods.

The implications of this research represent a paradigm shift in how cell culture can be approached within the cellular agriculture sector. As the demand for cultivated meat and advanced cell therapies continues to rise, the ability to use synthetic alternatives that offer greater stability and consistency could significantly enhance production capabilities.

The study, funded by The Cultivated B GmbH, reflects a growing trend within the industry to innovate and optimise cell culture methodologies. As companies seek to scale operations, the adoption of synthetic growth factors may become increasingly essential to meet market demands while ensuring product quality.

The discovery of TCB-32 and its analogs presents a promising avenue for enhancing cell culture practices. This research not only addresses existing challenges associated with bFGF but also underscores the potential for synthetic molecules to revolutionise the production of cell-based products.

Continued exploration and validation of these findings will be crucial for their integration into commercial applications, paving the way for a more sustainable and efficient food future.