StemCell Therapy

There are plenty of reasons to want to shift away from eating meat: its better for the planet and certainly better for animals that would otherwise be eaten. But meat is still a big draw, both in the U.S. and increasingly in medium-income countries like China.

At the Tufts School of Engineering, a team of scientists led by Professor David Kaplan is exploring another avenue to feed this trendmeat grown directly from animal cells. It could be the start of an entirely new agricultural industryas humane and green as plant-based meat substitutes, but providing taste, texture, and nutrition that is even closer to the experience of eating real meat.

The technology is already familiar to cell biologistsgrowing and harvesting cells from a single sample of tissue from a live anesthetized animal, but doing it in ways that may help the cells transform into something similar to the muscle tissue people enjoy eating from beef, chicken, and fish, including shrimp and scallops.

Meat from animals contains connective tissue, vascular networks, fat, and other cell types, as well as blood, biological fluids, and a complex mix of proteins and sugars, all of which contribute to the unique taste and texture of the meat. Replicating that structure and content is the technical challenge that the Tufts team is working on using the tools of tissue engineering.

A variety of flavors and textures can be achieved by growing different types of cells together, like skeletal muscle, fat cells and fibroblasts (the most common type of cell in connective tissue), adding nutrients to the surrounding media (the soup in which the cells grow), or using genetic modification to add components that not only introduce flavors, but can modify color or even improve on the nutritional quality of natural meat.

Andrew Stout, a doctoral student in biomedical engineering, has explored adding myoglobin to the cell growth media, for example. Myoglobin, a natural component of muscle, is a protein that carries iron and oxygen, and is associated with the bloody flavor of meat. He found that its addition to the mix helps improve the color of the cell mass, and even enhanced the growth rate of the meat substitute.

Stout has also been working to enhance the nutritional content of cell-based meat. In a recent journal publication, he reported how he had modified muscle cells from cows by genetically adding enzymatic machinery to produce the antioxidants phytoene, lycopene, and beta-carotene, normally found in plants.

Think of it as a way to make cell-based meat more plant-like in the healthy nutritional components it offers. Adding beta-carotene, for example, could have protective effects against colorectal cancer, which tends to be more prevalent among those with a high intake of red meat. Another benefit of this type of metabolic engineering is that the antioxidants could improve the quality and shelf-life of the meat.

How far can they take this nutritional engineering? I think other nutrients would definitely work, said Stout. Thats one of the things that I am the most excited about. Putting plant genes into mammalian cells is pretty un-travelled scientific territory, and so theres a lot of space to explore other nutrients, flavor, and color compounds. In addition, he adds, the cell-based meat can be engineered as a therapeutic food.

Most cell-based approaches have emulated processed meat such as hamburger, sausage, and nuggets. Replicating the appearance and texture of whole cuts of meat, like steak, is a different kind of challenge.

Tissue engineering experts in the Kaplan lab bring a lot of experience to the task of aligning cells and creating fibers resembling real meat structure, using things like mechanical tension and micropatterned substrates to help align cells into fibers.

Natalie Rubio, a Ph.D. student in biomedical engineering, found that switching from cows to caterpillars as a source of cells can have some advantages. The muscle and fat stem cells originating from the eggs of the tobacco hornworma beefy little caterpillarcan be used to generate tissue that resembles other invertebrates that were used to eating, like shrimp and scallops.

A vast amount of knowledge has already developed around large scale invertebrate cell culture, since insect cells are widely used in the production of pharmaceuticals. Suspended in a liquid medium, they tend to grow to very high density and have simpler requirements for maintenance and growth. Yields could be greater and production costs lower than from mammalian cells.

But Rubio explains that there is a very important step remaining to transform a soup of cells into something resembling real meatproviding a scaffold to shape and orient the cells.

The scaffold is the backbone of the meatit provides structure and texture, said Rubio. If we did not have that support structure, the meat would just look like slime.

Rubio generates scaffolds from chitosana polymer found in a closely related form (chitin) in exoskeletons such as crab shells and fungi. Chitosan is a great material to make scaffolds from because it is edible, abundant, and inexpensive, she said.

Chitin can be isolated from fungi and easily converted to chitosan and then formed into films, fibers, or sponges to act as scaffolding for cell culture. Rubio grows insect muscle and fat cells on the chitosan scaffolds to generate small, structured meat constructs.

Kaplans lab has been a hub and catalyst for cellular agriculture research and development in the academic sector for many years, he said. That continues with an annual course for undergraduates on cellular agriculture, which is again being offered this spring semester.

Cell-based meat has not yet been commercialized, but the first cultured beef burger was produced by Maastricht University in 2013, and a number of start-up companies are now working to create new products to sell.

Alumni from our group have fanned out across the globe to help create the foundation of a nascent cell-based agricultural industry, Kaplan said. They include Laura Domigan, who is a principal investigator at University of Auckland; research scientist Amanda Baryshyan at Gloucester Marine Genomics Institute; Ryan Pandya, CEO of Perfect Day Foods; Viktor Maciag, head of tissue engineering at Mission Barns; and Robin Simsa, CEO of Legendary Vish.

Mike Silver can be reached at mike.silver@tufts.edu.

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