The Scientist - USA (2022 - Spring)

SPRING 2022 | THE SCIENTIST 69

muscle or fat cells in vitro. Lucy Lee,

an expert in fish cell culture at the Uni-

versity of the Fraser Valley in Canada,

explains that the selection step is criti-

cal. The choice of cell line will determine

the taste of the cultured meat as well as

the technical parameters—time, tem-

perature, and nutrients, for instance—

needed to grow the cells on scaffolds or

other structures to produce a 3D prod-

uct, says Lee, who advised the Califor-

nia-based company Finless Foods on the

development of a tuna muscle cell line.

Researchers also have to look for cells

that can grow continuously. To make any

cultured meat sustainable, a cell line

ought to grow and maintain particular

features—including cells’ shape, size,

and ability to differentiate into different

types—forever, so that researchers don’t

have to keep starting over. This works

for some cell lines: Lee’s group has been

growing the same line of muscle cells

from killifish—a small fish that’s not very

good to eat but is great for research due

to its short lifespan—since at least 2014.

But other organisms have proved trick-

ier. “I haven’t been able to grow shell-

fish cell cultures continuously,” she says.

“Although I can get them to grow a long

time, they sort of die off after about nine,

ten passages”—one passage being a cul-

turing step where cell samples are har-

vested and transferred to a new culture

dish with fresh media. “That’s one big

struggle that people are still working on.”

To address this issue, UK-based cul-

tured meat biotech HigherSteaks Ltd is

focusing on induced pluripotent stem

cells (iPSCs), which, like other stem

cells, have no problem dividing indefi-

nitely. These cells “have huge growth

potential,” explains Ruth Faram, the

company’s chief scientific officer.

Using iPSCs has other advantages for

cell agriculture, too: it allows research-

ers to produce multiple tissue types from

a single cell line. “When you think about

what meat is, it’s not just muscle, it’s not

just fat, it’s a concoction of cells,” Faram

says, adding that a single iPSC can be

nudged with growth factors and molec-

ular signals to become either muscle or

fat. At the moment, she says, her team is

most excited about an iPSC line devel-

oped in-house by reprogramming a sam-

ple collected noninvasively from a pig.

The work at HigherSteaks is still in the

development phase, but Faram says that

the group’s cell line differentiates well

into muscle and fat.

It’s unclear how widespread the iPSC

approach is more generally, as compa-

nies don’t typically share this informa-

tion publicly. In a summary from the

Good Food Institute curating 47 com-

mercially available or in-development

cell lines appropriate for use in cellular

agriculture, however, only a handful are

classified as stem cell–like, while the rest

are proliferative cells committed to a cell

fate such as muscle or fat.

Meating market demand

Making cultivated meat viable on a com-

mercial scale carries challenges beyond

those associated with regular cell culture.

Typically, cells in culture grow affixed to

flat dishes, but in order to get to the vol-

ume needed for eventual commercializa-

tion, the goal is to use bioreactors, vessels

with a capacity of 200,000 liters or more in

which the cells grow in liquid suspension

containing nutrients and growth factors,

and often small beads, or microcarriers,

made of gelatin, glass, or plastic that the

cells can adhere to.

Scaling up comes with an accompanying

problem: cost. “In my lab, I can produce, in

a test tube, maybe a gram of cells,” explains

Lee, who is currently working with a rain-

bow trout muscle cell line. (She says that

she has tasted it and “it does taste like fish.”)

But “that’s a tiny, tiny little sample.... When

you add up the culture ingredients, the time,

the supplies, it’s about five hundred dollars

a gram. So who’s going to buy rainbow trout

for five hundred dollars a gram?”

One of the most expensive parts of cul-

turing cells in the lab concerns the choice

of growth media, which typically contain

nutrients, vitamins, minerals, growth fac-

tors, and proteins. The source of many of

these components in traditional cell cul-

ture media is fetal bovine serum. Lexi

Duscher, a molecular biologist who works

with Ovissipour at Virginia Tech, explains

that this serum costs up to $800 per liter

and also comes with other issues, includ-

ing variability and ethical questions about

how it’s sourced.

According to Bomkamp, there are

some serum-free options out there that

could avoid the variability and ethical

issues. But “the serum-free formulations

that exist are [mostly] coming from the

pharma industry” for growing cell lines

while controlling as many variables as pos-

sible, she adds. “They’re not produced with

food-compatible cost structures in mind,

so of course they’re expensive.”

Even with the best serum-free media,

though, most cells won’t grow as quickly

as those cultured with serum, because

the level of nutrients, vitamins, and min-

erals is lower. This in itself can bump up

costs: “For cultured meat... the longer it

takes for the cells to divide, the longer the

process will take, the more money it will

cost, and then ultimately the end product

will be much more expensive,” says Mar-

tina Miotto, chief scientific officer and

cofounder of CellulaREvolution, a UK-

based biotech working on improving cell

culture for cultivated meat and biomed-

ical applications. Finding cells that grow

well in serum-free conditions is essential,

Miotto explains, which reinforces the need

to choose starting cells carefully.

The team at CellulaREvolution is work-

ing on a bioreactor that will allow simul-

taneous harvest of cells while prolifera-

In 2020, financial investment in the area passed $350 mil lion—

double the investment of all previ ous years combined.

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