Cultured Meat Produced Using Immortal Stem Cells
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Scientists at Tufts University Center for Cellular Agriculture (TUCCA) have published a new method for generating immortalized bovine muscle stem cells (iBSCs) in ACS Synthetic Biology. The cells, which grow rapidly and can differentiate into mature muscle cells, may offer a solution to the scale-up bottlenecks associated with the production of cultured meat.
Difficulties when scaling-up cultured meat production
As “lab-based” or “cultured” meat makes strides towards our dinner plates, a lingering bottleneck for developers is how to scale-up production. That’s because the starting material for such products is typically muscle stem cells obtained through biopsy from an animal such as a cow, fish or chicken. These cells are cultured and grown in large quantities within a bioreactor. The efficiency of this method is limited by the fact that muscle stem cells divide just 50 times on average before they are no longer viable.
“Typically, researchers have had to do their own isolations of stem cells from animals, which is expensive and laborious, or use model cell lines from less relevant species, like mouse muscle cells,” says Andrew Stout, a graduate student in biomedical engineering at TUCCA.
For lab-grown meat to achieve its potential as a sustainable large-scale solution to food shortages and to climate change, scientists must find a way to expand muscle cells efficiently and consistently from relevant animal species in vitro. Immortalized stem cells – cells that have been engineered to proliferate indefinitely and can be cultured for long durations – could be the answer.
Stout is the first author of a new study from TUCCA where scientists have developed iBSCs from regular bovine stem cells.
Immortalized bovine cells rapidly grow and divide
A tell-tale sign of cellular aging is the shortening of telomeres, a repetitive DNA region found at the end of a chromosome. Telomeres carry protective functions, often likened to “caps” that prevent DNA degradation. As a cell undergoes multiple rounds of division, telomeres become shorter, which adversely affects their protective function. To promote the bovine stem cells’ “youthful” chromosomes, the researchers engineered constitutive expression of the ribonucleoprotein polymerase telomerase reverse transcriptase (TERT), which maintains telomere ends. Through constitutive expression of this polymerase, the iBSCs constantly rebuild their telomeres.
What is constitutive expression?
Constitutive expression refers to the continuous and uniform expression of a gene or protein. This can occur naturally in some cells but can also be engineered to occur through genetic manipulation.
Stout and colleagues also engineered for constitutive expression of the protein cyclin-dependent kinase 4 (CDK4), a modulator of a critical step in cell division, “turbocharging” the cells to divide and grow faster. “These cells achieve over 120 doublings at the time of publication and maintain their capacity for myogenic differentiation,” the researchers write.
Myogenic differentiation is a process through which stem cells differentiate into mature muscle cells. This is an important step when producing lab-based meat, as the final product must reflect the variety of muscle cells that are found in a piece of meat from an animal, influencing the flavor and texture of the meat. The researchers found that the iBSCs produced by their method did differentiate into mature muscle cells, however these cells were not identical to animal muscle cells, or the mature muscle cells obtained through conventional cultured meat production processes.
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“It’s possible that they are matured enough to replicate the flavor and texture of natural meat,” says Stout. “That’s something we will have to explore further. They are doubling at a very rapid rate, so they might just need a little more time to reach full maturity.”
Are the immortalized stem cells safe to ingest?
Questioning whether it’s safe to ingest cells that can indefinitely proliferate? The research team emphasize that once these cells have been harvested, stored, cooked and digested, they cannot continue to grow: “Like natural meat we eat today, the cells simply become inert material that we hope will taste delicious and provide a wide range of nutritious benefits,” says Dr. David Kaplan, Stern Family Professor of biomedical engineering at Tufts and director of TUCCA and lead author of the study.
Stout and colleagues are confident their immortalized cells offer a “valuable tool to the field” that will enable further research and development for advancing cultured meat.
Reference: Stout AJ, Arnett MJ, Chai K, et al. Immortalized bovine satellite cells for cultured meat applications. ACS Synth Biol. 2023. doi:10.1021/acssynbio.3c00216
This article is a rework of a press release issued by Tufts University Center for Cellular Agriculture. Material has been edited for length and content.