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The burgeoning cultivated meat industry is progressing toward commercialized products as food innovators worldwide gain regulatory approval for cell-based products. However, one of the main sticking points holding back progress is the cost of serum, a crucial component of cultivated meat. Now, researchers in Tokyo, Japan, are making waves by using photosynthetic microorganisms to create a self-purifying, nutrient-circulating system for eco-friendly cultured meat production.

The team has developed a system where growth factor-secreting liver cells and photosynthetic microorganisms can be grown together.

They claim this creates an environmentally friendly medium for growing muscle cells without using animal serum (the liquid part of the blood from animals) while also lowering costs.

Ethical concerns over serum

Alongside the high costs associated with using animal serum to promote cell growth, its use can be tied to the risk of contamination. Moreover, using animal serum raises ethical concerns.

This has prompted innovation in the space, with companies and research teams focusing on culture methods that allow muscle cells to grow without the use of serum.

The scientists co-cultured rat liver cells with modified cyanobacteria and the supernatant was used to promote muscle cell growth without serum (Image credit: Waseda University).

A research team led by professor Tatsuya Shimizu from Tokyo Women’s Medical University, along with Ph.D. student Shanga Chu and professor Toru Asahi from Waseda University, professor Yuji Haraguchi from Tokyo Women’s Medical University and professor Tomohisa Hasunuma from Kobe University, have developed a new system for culturing muscle cells without serum by using photosynthetic microorganisms.

Typically, animal serum provides proteins (growth factors) vital for muscle cell growth. However, rat liver cells are also known to secrete these growth factors.

The researchers found that the medium remaining after culturing these liver cells (or the supernatant) contains growth factors and can support muscle cell growth without using serum.

“Although more growth factor-secreting cells and longer cultivation produce larger amounts 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,” explains Shimizu.

The research team says that waste removal is key to improving the performance of this culture supernatant as an alternative to animal serum.

They 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 animal cells (rat liver cells and muscle cells), such as pyruvate and amino acids.

What happened in the study?

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

According to their findings, co-culturing cyanobacteria with the rat liver cells resulted in a 30% reduction of lactate and over 90% reduction of ammonia.

The nutrients produced by the cyanobacteria reduced the nutrient depletion by rat liver cells, resulting in an abundance of nutrients such as 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, the growth rate of the cells was three times higher than that seen when only rat liver cells were used.

This shows that co-culturing cyanobacteria significantly enhances the performance of the culture supernatant as a serum alternative and optimizes cell culture through waste upcycling.

“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,” continues Prof. Shimizu.

“Further, as a technology for producing meat without killing animals, culturing animal cells with photosynthetic microorganisms could help address not only future food security challenges but also ethical concerns and issues related to climate change.”

Moving animal serum use in cellular agriculture

The Good Food Institute (GFI) says animal serum will not be used in large-scale production of cultivated meat and a transition away from animal sources such as serum is underway within the nascent sector.

“The use of animal-derived components in cultivated meat production has prohibitive economic and ethical constraints. Many companies have already publicly stated they are using medium formulations that are entirely animal-free, with some research groups and companies having published their protocols for serum-free proliferation and differentiation,” the GFI says.

In Singapore, Eat Just’s first cultivated chicken products were produced using small quantities of fetal bovine serum (FBS). However, the company received approval to sell cultivated chicken using serum-free media in January 2023.

Upside Foods submitted information to the US FDA showing that their product can be created with or without FBS. In processes without FBS, purified bovine serum albumin was used. However, the company has stated that it intends to phase out the use of bovine serum albumin with recombinant forms of albumin protein.