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Bovine cells engineered to produce their own growth factors in cultured meat production

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Cultured meat requires growth factors for cell development. These are typically added to cell culture media at considerable cost, impacting commercial potential. New research has shown that edited bovine cells can produce their own growth factors, eliminating the need for costly additions to media, FoodNavigator reports.

A complex process

Cultured meat production is a complex process. In many parts of the world, regulatory approval has not yet been obtained. One of the main barriers to commercialization is cost, with one of the main costs being the use of growth factors.

Growth factors cannot be easily eliminated: they are one of the most important parts of cultured meat production, as they stimulate cell growth. To promote growth, they must be added to the cell culture medium, the nutrient mix that cultured meat requires to function.

However, they are also very expensive and one of the main reasons why cultured meat producers find it so difficult to produce at consumer-friendly prices.

Now, a new study published in the journal Cell Reports Sustainability shows that bovine cells can be engineered to create their own growth factors, eliminating the need to add expensive growth factors to the cell culture medium. This has the potential to be an advantage for the industry.

"These types of systems offer the potential to drastically reduce the cost of cultured meat production by enrolling the cells themselves to work with us in processes, requiring fewer external inputs (added ingredients), and therefore fewer secondary production processes for these inputs," lead researcher Andrew Stout told FoodNavigator.

The role of growth factors in serum-free media

Growth factors are necessary because they provide a signal for cell growth and differentiation. Fibroblast growth factors (FGF), for example, trigger the growth of skeletal muscle cells. Without such a growth factor, cell growth decreases. However, they are often a very costly part of cell culture media and need to be frequently replenished.

For example, a culture medium for immortalized bovine satellite cells (iBSC), Beefy-9, relies on fibroblast growth factor 2 (FGF2), an expensive growth factor. After another costly component, protein albumin, was replaced with rapeseed meal, FGF2 remained the single most costly element, contributing to about 60% of the cost.

"At present, the price is high because fibroblast growth factors (FGF) are recombinantly produced, whereby bacteria are engineered to produce the proteins and then harvested from those bacteria," Stout told us.

"This involves a completely separate bioprocess where the bacteria are grown in large tanks to produce the growth factors, as well as costly harvesting and purification steps. It is essentially a second upstream 'grown factor process' that is necessary to be able to feed into the 'cultured meat' process."

"A large part of the costs comes from that purification part, but there are also inherent costs to bacterial culture. It is certainly possible for recombinant protein production to be cheaper for FGF today, but the current scale and production methods are still very expensive, and there will always be certain costs for highly processed factors that are added as ingredients rather than bovine (or other meat) cells making their own."

Engineering with lower costs

To eliminate the need for such costly growth factors, researchers engineered the iBSCs to develop their own growth factor, meaning they did not require the expensive addition of growth factors to serum. These cells were able to proliferate in a cell culture medium without FGF2, dramatically reducing the cost of the production process.

"We inserted the gene for bovine FGF into the cells' genome in front of a promoter (a piece of DNA that helps speed up protein production from genes) that we can activate or deactivate by adding a specific chemical to the cell culture."

"In other words, using the chemical as a switch, we can make the stem cells produce a lot of FGF and then stop production when we need to. This is important because after we induce the stem cells to grow with FGF, we need to turn off FGF so that the cells can focus on transforming into mature muscle cells," Stout said.

However, the process is not yet ready for commercialization due to reduced growth and differentiation rates for the modified cells.

However, the process has a lot of potential. In theory, Stout suggested, it could be used to cultivate chicken, fish, and cultured pork meat. It also has sustainability benefits.

"It is likely that the process will improve environmental values, as you no longer need the entire secondary recombinant growth factor production process (which uses energy, resources, etc.) to support cultured meat production," Stout said. (Photo: Freepik)

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