Scientists from Tokyo Women’s Medical University in Japan have developed a system where growth factor-secreting liver cells and photosynthetic microorganisms can be grown together to create a low cost, environmentally friendly medium to grow muscle cells without the use of animal serum.

The researchers use photosynthetic microorganisms to create a self-purifying, nutrient-circulating system for eco-friendly cultured meat production.

Usually, animal serum provides proteins called growth factors that are essential for the growth of muscle cells. However, rat liver cells are also known to secrete these growth factors. The researchers discovered that the medium remaining after culturing rat's liver cells (or the supernatant) contains growth factors, and can support muscle cell growth without the use of serum.

“Although more growth factor-secreting cells and longer cultivation produce larger amount of growth factors, the downside is that the cells also produce waste products like lactate and ammonia into the medium at the same time, which eventually hinders muscle cell growth,” research team leader Professor Tatsuya Shimizu explained.

This means that waste removal is crucial to improve the performance of this culture supernatant as an alternative to animal serum. To resolve this, the researchers developed L-lactate assimilating cyanobacteria (photosynthetic microorganisms) with lactate to pyruvate converting genes, which were capable of taking in harmful waste metabolites, such as lactate and ammonia, and converting them into nutrients for rat liver cells and muscle cells, such as pyruvate and amino acids.

In the study, the research group proposed a new system in which the growth-factor secreting rat liver cells would be co-cultured or cultured together with the modified cyanobacteria, and the supernatant from this co-culture could then be used to promote muscle cell growth without serum.

They found that co-culturing cyanobacteria with the rat liver cells resulted in a 30% reduction of lactate and over 90% reduction of ammonia. Additionally, the nutrients produced by the cyanobacteria were able to reduce the nutrient depletion by rat liver cells, resulting in an abundance of nutrients like glucose and pyruvate in the co-culture supernatant compared to the supernatant collected from where rat liver cells were grown alone.

When this co-culture supernatant was used to cultivate muscle cells, they found that the growth rate of muscle cells was three times higher than the growth seen when only rat liver cells were used, demonstrating that co-culturing cyanobacteria can significantly enhance the performance of the culture supernatant as a serum alternative and optimises cell culture through waste upcycling.

Shimzu concluded: “Our study provides a novel low cost, sustainable cell culture system with broad applicability in various fields involving cellular agriculture, such as cultured meat production, fermentation, bio-pharmaceutical production and regenerative medicine”.

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