Could ProFuse Technology’s cocktail of small molecules help transform the cultured meat economy?

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While there are many ways to improve the unit economics of cultured meat, from reducing the cost of producing expensive growth factors used in cell culture media, to exploring ways to recycle media , through the development of more efficient cell lines; ProFuse Technologyattacks the process of skeletal muscle tissue formation (myogenesis) so businesses can produce more meat, faster.

Accelerate the process of skeletal muscle formation

The first phase of the myogenesis process begins with rapid cell division and multiplication (the proliferation phase) of myoblasts (muscle stem cells) in a nutrient-rich medium.

In the second phase (differentiation phase), the myoblasts stop dividing and begin to differentiate by fusing to form nascent myotubes (development of tubular-like muscle fibers). Then, in a secondary fusion stage, these small myotubes begin to fuse with myoblasts to form larger myotubes, which eventually mature into muscle fibers (the maturation phase).

“We found a way to improve the signaling process so it happens bigger and better”

Typically, to move from the proliferation phase to the differentiation phase, companies will reduce the growth factors in the medium and the cells will stop dividing in this “depleted” or “reduced” medium and gradually begin to differentiate and mature.

Depending on the species, this phase of differentiation and maturation can take days or even weeks, and is not always super efficient, as only a certain percentage of myoblasts will fuse to form muscle fibers in a production cycle. given, says ProFuse Technology, which was formed last summer to apply the science developed at the Weizmann Institute of Science​.​

By administering a cocktail of small molecules (a medium supplement) that target a molecular signaling pathway regulated by an enzyme called ERK, ProFuse effectively triggers a biological switch that immediately triggers the differentiation of all myoblasts and activates another protein (CaMKII or ‘Cam kinase’) which is involved in the secondary fusion phase, where small myotubes fuse with myoblasts to create larger muscle fibers, co-founder Tamar Eigler-Hirsh, PhD, told FoodNavigator-USA.

“It’s the natural process of myogenesis to activate cam kinase, so it happens naturally, butwe found a way to improve the signaling process so that it happens bigger and better.

VIDEO​: The video above, courtesy of Dr. Tamar Eigler-Hirsh, shows muscle stem cells under the microscope: “When exposed to a molecule that blocks the ERK enzyme (right panel), cells differentiate and undergo massive fusion…”

“Not only are we speeding up the process, but we are also increasing the degree of differentiation and the degree of fusion”

For poultry cells, in a laboratory environment at least, ProFuse’s medium supplement can reduce the duration of the differentiation and maturation stage from seven days to three days, and cause the muscle fibers to “bulk up” more, thus improving protein and texture at the same time. , which could have exciting implications for the cultured meat industry if these effects can be replicated in an industrial setting, Dr. Eigler-Hirsh said.

“All we do is add our extra media, and we’re able to start that process much earlier, so already 24 hours after the treatment you can see the start of muscle fiber formation. And if you look at the endpoint at 72 hours after treatment, we have reached a maximum threshold.

“Significant increase in protein content”

If you just miss the growth factors and don’t add ProFuse’s multimedia supplement, she said, the differentiation “still take place, it will just be much less effective. There is a maximum capacity you can get just by reducing the serum. Where common practice is around 10%, we get around 60% efficiency in the process. »

Without ProFuse, she claimed, “Youwould never reach that 60% fusion threshold, it just doesn’t happen. »

She says: “So not only are we speeding up the process, we’re also increasing the amount of differentiation and increasing the amount of fusion, and we’ve tested it on mouse, chicken, bovine, and sheep cells with similar effects on four species, and we’re now just diving into fish.

Undifferentiated myoblasts that did not fuse during the first production cycle still have the ability to convert into muscle in future production cycles, but there are clear advantages to increasing the fusion index the first time around, she said, noting that ProFuse Technology’s small molecules reduce the number of production cycles required, and improve meat production in each cycle, improve muscle fiber quality and increase meat content. in protein.

In the data we acquired from chicken cultures, using ProFuse, the muscle fibers are larger; we get about a four and a half times increase in protein content using ProFuse compared to standard practice…and we see similar data in cattle ​[muscle tissue].”

ProFuse Tech’s technology is based on a six-year study by the Weizmann Institute of Science led by Professor Eldad Tzahor (right) – an expert in the field of embryonic development and cell regeneration; Dr. Ori Avinoam (center) who specializes in intercellular fusion and tissue formation; and Dr. Tamar Eigler (left) who specializes in muscle stem cell biology. Image credit: Weizmann Institute

A word of caution: lab scale versus commercial scale

Before we start opening the champagne, however, it’s important to point out that all of these numbers could change drastically in an industrial setting, warned co-founder scientist Professor Eldad Tzahor.

“It is important to remember that what we are talking about here is based on basic research in the laboratory, not in an industrial setting. Every company and every cell type is different, and we haven’t tested this in a 10,000 liter bioreactor or 3D printing environment etc.

Collaboration with cultured meat startups

So what happens next?

“Probably in a few months” said CEO Guy Nevo Michrowski“We will announce our Generation Two cocktail.”

Meanwhile, he said: “We are engaged in a collaboration with some of the cultured meat companies, testing the effectiveness and effect of our cocktails in their production environment.”

Regulatory status

Asked about the regulatory status of the small molecules in the ProFuse cocktail, he replied: “The big challenge is regulation, but we’re very optimistic that we’re going to be considered GRAS material in the US or some sort of processing aid in other countries early next year.

“When you test the residual level in the ​[final] meat product, it is extremely weak to almost undetectable.

GFI: “Having full control over the skeletal muscle differentiation pathway is an important scientific advance”

Asked about the significance of ProFuse Technology’s work, Elliot Swartz, PhD, senior scientist, cultured meat, at the Good Food Institute, told FoodNavigator-USA that his data and results were “impressive.”

He added: “Having full control over the skeletal muscle differentiation pathway is an important scientific advance. Skeletal muscle differentiation is typically a fairly slow process (days to weeks), and the ProFuse additive significantly reduces this time, which could translate to cost savings, as shorter lead times mean less bioreactors and fewer media will be needed to create a given amount of cultured meat.

Meanwhile, as the muscle fibers “swell” faster“meaning that amino acids are efficiently converted into biomass”, he said“This in turn could translate to better protein and nutrient content as well as texture for structured products.”

Another important factor, he added“is that the additive is still effective in an otherwise growth medium formulation. This means that cultured meat manufacturers can easily achieve differentiation without drastically changing the media formulation. In general, a less complex medium is likely to be desirable for supply chain and other practical considerations.”


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