CM logo no tag no bg HR.png
health 101 bg_1.png

The Process

How Is Cultivated Meat Made?

Cultivated meat is made by replicating the biological process of cell growth. The production method is called cellular agriculture.

101

The Process 101

Scroll

Down

 

Animal agriculture is the production of food and materials by breeding, raising, and slaughtering animals.

Cells grow inside an animal. Animals are provided water and feed to grow. The nutrient-rich feed contains energy, proteins, vitamins, and minerals. The animals’ organs produce growth stimuli. Cells multiply and mature inside an animal.

An explanation of meat production methods for conventional meat and lab grown meat

After the animal has grown to the desired size and characteristics, the animal is slaughtered. The meat then undergoes food processing, packaging, and finally, is sold.

Researchers choose the best genetic lines and selectively breed animals. Animals become pregnant and then give birth.

Cells grow inside a cultivator. Cells are provided water and feed to grow. The nutrient-rich liquid feed contains energy, vitamins and minerals, proteins, and growth stimuli. Cells multiply and mature inside the cultivator.

After the meat in the cultivator has grown to the desired size and characteristics, the meat is harvested. The meat then undergoes food processing, packaging, and finally, is sold.

An initial small sample of cells is collected from a healthy living animal. The best starter cells are stored in cell banks for use in production.

Cellular agriculture is the production of food and materials by directly cultivating cells.

Hover over a category

on the graphic

“How Cultivated Meat Is Made” by WhatIsCultivatedMeat.com can be reused under the CC BY 4.0 license.

 

201

The Process 201

 
1-how-is-meat-made-mobile 21-07.png
Cellular agriculture

Cellular agriculture is the production of food and materials by directly cultivating cells.

Cultivated meat is a product of cellular agriculture. The end product — meat — is the same, but the production method differs significantly.   Cultivated meat does not require breeding, raising, or slaughtering animals.

Instead, meat cultivation (the production of meat using cellular agriculture) is the process of growing cells from an animal in a cultivator. A cultivator (also known as a bioreactor) is a vessel that provides a temperature-controlled, clean, and closed environment for the cells to grow into meat.

Meat cultivation is a process of biomimicry. Biomimicry is a practice of learning from nature and then developing technologies that mimic natural processes. In the case of cellular agriculture, the natural cellular growth processes that happen inside an animal are replicated outside of the animal.

Starter cells

Theoretically, we could make cultivated meat using cells from any animal.

The first step in meat cultivation is to obtain a sample of cells from an animal. These cells could theoretically come from any animal species or breed. Some scientists are focusing on specialty or heirloom breeds within a species (such as Wagyu beef). Most companies are working on species that are already commonly bred for human consumption, while others are researching cells from a multitude of species in the search for optimal growth potential and taste. Cell samples can be collected without causing harm to the animal.

Companies select starter cells for optimal production.

Meat is made of muscle and fat (and can also include connective tissue, blood vessels, skin, and bone).

For optimal production, starter cells should:

  • Consistently grow and duplicate easily

  • Be able to mature into the different cells types that make up meat

  • Produce meat with excellent taste and nutritional profile

Currently, most starter cells are sourced from living animals.

The most common method for obtaining cells is to take a small, harmless muscle biopsy or skin sample from a healthy living animal. However, some companies might collect cells from animals after they have been slaughtered for conventional meat production—this may be important for religious certifications. Another exception is sampling cells from fish and other sea animals, which would be difficult because they live under water. Academic researchers and companies use these samples of animal cells to select cell populations (e.g., muscle or fat) with specific and uniform characteristics for consistent meat production.

In time, most starter cells will be sourced from cell banks.

Storing the cells (called cell-banking) and making cells available for academia and industry will be a necessary step for advancing research and production to a larger scale. Cell banks screen and certify cells for quality, and then store them at very cold temperatures until they are needed to start production. These banks will house a variety of species and cell types suitable for cultivating different products.

Optimizing starter cells is an important research area.

Embryonic stem cells are one potential type of starter cell.

Embryonic stem cells are useful for cultivation because they multiply easily and can grow into any kind of cell. These cells come from embryos that are a few hours to a few days old, called ‘blastocysts’. Blastocysts are made up of about 100 cells. For example, to collect the embryos from a cow, a veterinarian flushes the uterus with a saline solution before the embryo has implanted in the uterine wall. For chicken, one simply collects the eggs. Embryonic stem cells can also be obtained from embryos produced by in-vitro fertilization.

Embryonic stem cells can multiply indefinitely and can develop into many different types of cells. However, they would require a more complex and expensive production process, as they tend to need specialized growth media and tighter controls in order to mature into the desired tissue types, such as muscle and fat.

Muscle, fat, or skin cells are other potential types of starter cells.

It is also possible to cultivate meat using cells collected from tissues such as muscle, fat, and skin. Cell collection typically involves a small muscle biopsy or skin scrape, both of which are harmless procedures that can be performed with local anesthesia.

Although muscle, fat, and skin cells don’t multiply as easily as embryonic stem cells, these mature cells (adult stem cells) can be reprogrammed to behave similarly to embryonic stem cells.   Reprogramming enhances their ability to duplicate, as well as their ability to become specialized cells.

Like embryonic stem cells, the reprogrammed cells can multiply indefinitely, and are able to form into any kind of specialized cell (like muscle or fat, both of which make up meat). Reprogrammed cells are called ‘induced pluripotent stem cells’.

Cell reprogramming can be accomplished by introducing a set of specific genes, proteins, or small molecules into the cells.   Using cell reprogramming techniques improves the producers’ ability to use cell samples taken from a live animal and ultimately create a more efficient and consistent production process. Researchers are also exploring the potential of these technologies to improve the nutritional profile of meat.

Starter cells are still being researched.

Importantly, the taste profile and efficiency of different starter cells is currently being researched, and we do not yet know which types of starter cells will ultimately be used for meat cultivation. It’s likely that some producers will not reprogram starter cells at all, while others will use reprogramming to improve the nutritional profile,   increase efficiency, or decrease the need to take cell samples from live animals.

Depending on the specific methods, cultivated meat that relies on gene editing could be considered genetically modified (GM). As with tomatoes, apples, and corn, we will likely have GM and non-GM cultivated meat. Due to current regulation, only non-GM cultivated meat is expected to be sold in the European Union.

Choosing starter cells from either a cell bank or a cell sample from any species of animal is the first step in cultivating meat. These cells can be embryonic stem cells or adult tissue cells. Research to identify which cell types are optimal for cultivated meat production is currently underway.

Cultivators

Cultivators provide the living environment for cells.

Cultivators, also known as bioreactors, are vessels that provide temperature-controlled, clean, and closed environments for cells to grow.

They are widely used in the food and biomedical industries to produce vitamins, beer, vaccines, insulin, enzymes, and other products. Cultivators have:

  • a heating and cooling system to control temperature

  • piping to deliver nutrients and oxygen and remove waste products

  • sensor systems to monitor the environment and to measure things like pH and oxygen

Cultivators are typically made of stainless steel or glass to allow for easy sterilization between batches. Disposable liners are another method for ensuring sterility.

Inside a cultivator, cells repeatedly duplicate, quickly increasing in number. The starter cells then mature into muscle and fat when attached to a solid material (called scaffolding). Piping carries liquid nutrients (called growth media or feed) and oxygen inside the cultivator to reach the cells and help them grow and mature.

In the field of medicine, specialized bioreactors are under development for the purposes of repairing or replacing heart tissue, skeletal muscle, blood vessels, ligaments, and more. Inside these specialized bioreactors, cells grow on “scaffolding” into specific configurations. For example, scaffolding helps heart cells grow into the desired shape and size of the necessary heart tissue.

Similarly, researchers are developing specialized cultivators (bioreactors) for cellular agriculture.   Companies are working to develop cultivation systems that produce meat with the same or more efficiency as large-scale conventional animal agriculture.      In the future, smaller systems could serve specific regions, or possibly even produce for a single restaurant.

Growth media

Growth media is the feed for cells.

Like all the other production steps for meat cultivation, feeding the cells involves mimicking the biological processes within an animal, outside the animal.

Inside the animal, blood delivers the components necessary for cell life and growth: carbohydrates, amino acids, proteins, fats, vitamins, minerals, and growth factors.

Inside the cultivator, growth media contain the same components:

  • Carbohydrates

  • Amino acids

  • Fats

  • Vitamins

  • Minerals

  • Growth stimuli (signaling molecules)

In combination, these components are crucial for cell life, whether in an animal or in a cultivator. The growth medium fosters cell growth, doubling, and differentiation into the many cell types that make up meat.

Cultivated meat production will use serum-free growth media.

In the biomedical field, cell culture has historically used serum (a nutrient-rich, high-protein component of blood, typically from fetal cows) as a growth media ingredient. The earliest cultivated meat research and development used fetal bovine serum (FBS) because alternatives were not yet available.

Importantly, cultivated meat producers are now focusing on developing serum-free growth media for use in meat production. Serum-free media contains many of the same components as FBS but is produced without animals, has a controlled and consistent nutrient composition, and is contamination-free.

Some specialized serum-free media formulations are already in use for certain biomedical applications. Similarly, cellular agriculture researchers are in the process of optimizing serum-free growth media for different types of species, cells, and growth conditions. Many companies have already accomplished this milestone.

Growth media components can be obtained from plant and fungus extracts, or produced through fermentation in the same way that many vitamins and medicines are produced.

Here are some specific examples of the many components in serum:

Proteins

  • The protein albumin has antioxidant properties and carries molecules, vitamins, fatty acids, and cholesterol

  • The group of proteins called transferrins deliver iron to the cells. Iron plays an important role in respiration

Lipids

  • Fatty acids are the building blocks of stored fat

  • Cholesterol is a structural component of the cell membrane

Protein-based growth factors (signaling molecules or hormones)

  • Insulin aids the transport of glucose

  • Thyroid-derived hormones influence cell growth

Trace elements (minerals)

  • Minerals such as sulfur, iron, chlorine, chromium, cobalt, copper, zinc, manganese, molybdenum, iodine, and selenium are essential to cell functioning

Serum-free media is quickly evolving for wide-scale production.

Serum-free media allows for a contamination-free and consistent source of nutrients, but is currently very expensive. In both the biopharmaceutical and cellular agriculture industries, much research is underway to develop nutrient-rich and inexpensive serum-free growth media tailored for specific applications. Some companies are specializing in serum-free media supplements or even the full formulation, which will enable wide scale cultivated meat production to become a reality more quickly.

Developing serum-free growth media is an important step for the cultivated meat industry to transition from research into production. Growth media enables the meat to contain the same (or nearly the same) components and nutrients as conventionally-produced meat.

Scaffolding

Scaffolding provides a structure for the cells to mature into muscle and fat, while allowing nutrients and oxygen to reach the cells.

Quality meat has desirable muscle and fat composition, texture, and product form. Within a cultivator, structures—called scaffolds—provide a surface for the cells to mature into muscle and fat, and into the desired texture and form.

Scaffolds help the cells grow into the desired meat product. A scaffold’s physical attributes (such as composition, function, stiffness, roughness, or porosity) can influence the characteristics of the final meat product. Scaffolding can be made of many types of edible biomaterials, such as gelatin, and derivatives of plants, algae, or fungi. Growth stimuli—molecules that signal cells to mature into muscle and fat—can also be introduced through scaffolding.

Smaller, less complex scaffolding is effective for cultivating ground meat, like meat used for burgers, sausages, and nuggets. More complex scaffolding is needed for cultivating meat with a specific structure and thickness, like steak. Scaffolding with a porous structure allows nutrients and oxygen to reach the cells inside thicker cuts of meat.

Inside a cultivator, scaffolding replicates the environment in which cells grow.

In meat cultivation, scaffolding is used to biomimic the natural cellular environment surrounding cells, called the ‘extracellular matrix.’ The extracellular matrix is an interlocking mesh of fibrous proteins (like collagen) and other substances necessary for cell function.

Cells are highly responsive to their environment. Whether inside an animal or inside a cultivator, the proteins in the extracellular matrix signal cells to multiply, to become specialized cells (muscle, fat), or to form a specific structure.

There are many types of scaffolding under development. Examples of scaffolding types include:

  • Microcarriers. These tiny edible or biodegradable beads are coated with proteins that encourage cell attachment. For production of ground meat, microcarriers are a relatively simple way to give cells the necessary surface area and environmental cues for cells to grow.

  • Decellularized plants (such as spinach leaves) and fungus (mushrooms). Plant and fungi materials serve as a scaffold upon which cells can grow into thicker structures.

  • 3D bioprinting. Cells are placed into formation layer-by-layer using a computer-aided design process. The result is a product with a very specific and customizable structure.

Harvest and processing

It could take about five to seven weeks to produce cultivated meat.

At the time of harvest, cultivated meat is the same as conventional meat. Researchers have already produced meat from a number of species through cellular agriculture. The list includes domestic and wild land animals (cows, bison, pigs, sheep, goat, chickens, duck, alpaca, kangaroo), and sea animals (salmon, mahi mahi, bluefin tuna, yellowtail, grouper, shrimp, lobster).

Production will likely take about five to seven weeks. The exact time will depend on species, type of cells, growing conditions, scale, and desired product.      The graph below shows the average production time under cultivated and conventional operations.

A comparison of production timelines for lab grown meat and conventional meats

For cellular agriculture, the average production time is estimated from the time of placing cells in cultivators to harvest. For animal agriculture, the average production time is calculated from the time of fertilizing the egg to slaughter (includes gestation time for cow or pig). “Production Timelines” by WhatIsCultivatedMeat.com can be reused under the CC BY 4.0 license.

2-production-timeline-mobile.png

Over time, producers will be able to harvest larger batches.

Harvesting cultivated meat will look different depending on the scale. As technologies improve, large companies could harvest batches by the ton (or more). In very large systems, the production time might be longer, since more time is needed for the cells to multiply in number (up to 14 weeks). Such centralized systems will likely mean that cultivated meat is produced more efficiently, and is as affordable as conventional meat. However, consumers may one day have access to regional, local or even in-home cultivators for specialty meat production.

Food processing

The last production step is food processing. Once cells are harvested from cultivators, they are processed, much in the same way as conventional agriculture. Processing could include forming the meat into shapes (burger patties, meatballs, nuggets), seasoning, and packaging.

Distribution and sale

Products could be sold as pure cultivated meat, or mixed with plant ingredients to create a blended product.

 
 
 
 
 
 

References

1- Zidaric, T., Milojevic, M., Vajda, J., Vihar, B., & Maver, U. (2020, August 20). Cultured meat: Meat industry hand in hand with biomedical production methods. Food Engineering Reviews, 12, 498-519.

2- Aberle, E. D., Forrest, J. C., Gerrard, D. E., & Mills, E. W. (2012, June 22). Principles of meat science (5th ed.). Kendall Hunt.

4- Bogliotti, Y. S., Wu, J., Vilarino, M., Okamura, D., Soto, D. A., Zhong, C., Sakurai, M., Sampaio, R. V., Suzuki, K., Izpisua Belmonte, J. C., & Ross, P. J. (2018, February 9). Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts. PNAS, 115(9), 2090-2095.

5- Choi, J., Lee, S., Mallard, W., Clement, K., Tagliazucchi, G. M., Lim, H., Choi, I. Y., Ferrari, F., Tsankov, A. M., Pop, R., Lee, G., Rinn, J. L., Meissner, A., Par, P. J., & Hochedlinger, K. (2015). A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs. Nature Biotechnology, 33, 1173-1181.

6- Fuet, A., & Pain, B. (2017). Chicken induced pluripotent stem cells: Establishment and characterization. Avian and Reptilian Developmental Biology, 211-228.

7- Schlaeger, T. M., Daheron, L., & Daley, D. Q. (2014, December 1). A comparison of non-integrating reprogramming methods. Nature Biotechnology, 33, 58-63.

8- Stout, A. J., Mirliani, A. B., Soule-Albridge, E. L., Cohen, J. M., & Kaplan, D. L. (2020, November). Engineering carotenoid production in mammalian cells for nutritionally enhanced cell-cultured foods. Metabolic Engineering, 62, 126-137.

9- Bellani, C. F., Ajeian, J., Duffy, L., Miotto, M., Groenewegen, L., & Connon, C. J. (2020, November 4). Scale-up technologies for the manufacture of adherent cells. Frontiers in Nutrition.

10- Hanga, M. P., Ali, J., Moutsatsou, P., de la Raga, F. A., Hewitt, C. J., Nienow, A., & Wall, A. (2020, June 22). Bioprocess development for scalable production of cultivated meat. Biotechnology and Bioengineering, 117(10), 3029-3039.

11- Allan, A. J., De Bank, P. A., & Ellis, M. J. (2019, June 12). Bioprocess design considerations for cultured meat production with a focus on the expansion bioreactor. Frontiers in Sustainable Food Systems.

12- O’Neill, E. N., Cosenza, Z. A., Baar, K., & Block, D. E. (2020, Dec 5). Considerations for the development of cost‐effective cell culture media for cultivated meat production. Comprehensive Reviews in Food Science and Food Safety.

13- Kolkmann, A. M., Post, M. J., Rutjens, M. A., van Essen, A. L., & Moutsatsou, P. (2019, December 28). Serum-free media for the growth of primary bovine myoblasts. Cytotechnology, 72, 111-120.

14- Freshney, R. I. (2005, October 14). Culture of Animal Cells.

15- Bodiou, V., Moutsatsou, P., & Post, M. J. (2020, February 20). Microcarriers for upscaling cultured meat production. Frontiers in Nutrition.

16- Verbruggen, S., Luining, D., van Essen, A., & Post, M. J. (2018). Bovine myoblast cell production in a microcarriers-based system. Cytotechnology, 70, 503-512.

17- Campuzano, S., Mogilever, N. B., & Pelling, A. E. (2020, February 24). Decellularized plant-based scaffolds for guided alignment of myoblast cells. bioRxiv.

18- Ben-Arye, T., Shandalov, Y., Ben-Shaul, S., Landau, S., Zagury, Y., Ianovici, I., Lavon, N., & Levenberg, S. (2020). Textured soy protein scaffolds enable the generation of three-dimensional bovine skeletal muscle tissue for cell-based meat. Nature Food, 1, 210-220.

19- Gershlak, J. R., Hernandez, S., Fontana, G., Perreault, L. R., Hansen, K. J., Larson, S. A., Binder, B. Y. K., Dolivo, D. M., Yang, T., Domino, T., Rolle, M. W., Weathers, P. J., Medina-Bolivar, F., Cramer, C. L., Murphy, W. L., & Gaudette, G. R. (2017, May). Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds. Biomaterials, 125, 13-22.

20- Modulevsky, D. J., Lefebvre, C., Haase, K., Al-Rekabi, Z., & Pelling, A. E. (2014, May). Apple derived cellulose scaffolds for 3D mammalian cell culture. PLoS One, 9(5).

21- Handral, H. K., Tay, S. H., Chan, W. W., & Choudhury, D. (2020, September 21). 3D printing of cultured meat products. Critical Reviews in Food Science and Nutrition.

22- Kang, D. H., Louis, F., Liu, H., Shimoda, H., Nishiyama, Y., Nozawa, H., Kakitani, M., Takagi, D., Kasa, D., Nagamori, E., Irie, S., Kitano, S., & Matsusaki, M. (2020, October 16). Engineered whole cut meats assembled of cell fibers constructed by tendon-gel integrated bio printing. Research Square.

23- Specht, L. (2020, February 9). An Analysis of Culture Medium Costs and Production Volumes for Cultivated Meat. The Good Food Institute.