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Cultured Meat: Teaching an Old Cell New Tricks

By Tannavee Kumar, Genetics and Genomics ‘20

 

Author’s Note

Cultured meat has been a topic of great discussion as we try to understand the extent to which animal agriculture contributes to greenhouse gas emissions and other environmental issues. While plant-based imitation meats have been on the market for decades, I was particularly interested in this lab-grown alternative when I heard that stem cells were being used to produce actual meat without having to raise animals themselves. This could potentially reduce the environmental footprint of the agricultural industry while providing a viable solution for consumers. While it is critical to understand how consumption levels of animal-based products have had an effect on health, and particularly how the change in consumption of these products have changed average human health, my research focused more on how traditional meat impacts environmental health and how cultured meat can help mitigate some of these problems.

Trends in Meat Consumption

Animals used for meat and other foods were first domesticated between 15,000 and 5,000 years ago [1,2] when this practice evolved into animal agriculture. The shift from a hunter-gatherer lifestyle to an agricultural one meant a steady and growing food supply. The increase in wealth, which fuels factory farming, usage of fertilizers, and technological and genetic advancements, have expanded food availability across various regions around the world, thus increasing consumption [3]. In the Mediterranean, mean availability of animal products such as meats, animal fats, fish and seafood increased from 268.4 kilocalories per person per day during the period of 1961-1965 to 531.1 kilocalories per person per day during the 2000-2004 period; similar trends were also seen for Northern and Central Europe [4].

Since 1963, consumption has been on the rise by a considerable 62 percent throughout the world, with the strongest increase in developed nations. In general, countries like the United Kingdom and United States were found to primarily source pigs, sheep, and cattle. Developing regions like the Middle East, Africa, and India mainly produced goat and camel meats; however, non-animal-based sources of protein were still found to be dominant [3]. Countries such as China and Brazil that have enjoyed economic growth also show ninefold and threefold increases, respectively, in meat consumption including cattle since 1963. Thus, researchers have found a strong correlation between economic growth and increased meat intake.  

John Kearney at the Dublin Institute for Technology expects food consumption to be on the rise through 2050 and claims trends show that meat will be no different. The major drivers of this forecast are food availability, accessibility, and choice. Disposable income, urbanization, globalization, marketing, religion, culture, and consumer attitudes are all causes of such drivers. After 1.7 billion livestock are raised, transported, and processed, 300 million tons of meat are produced every year [6,8].

 

Environmental Impact

Increased consumption of animal-based products proves to have major environmental consequences due to its inefficient process. Meat production requires significant inputs of land, water, food, and energy to support multiple steps. The process begins with growing sufficient crops to feed livestock; an estimated 75 percent of the world’s agricultural land goes into meat production [6]. In Central America alone, 40 percent of rainforest land has been cleared in the last 40 years for cattle pasture to meet the demands of the export market — often times the United States [7]. Furthermore, Harold Mooney from Stanford University’s Woods Institute estimates that one-third of the world’s total arable land is utilized to support livestock in some shape or form [8]. Over time, the land is depleted from wind and soil erosion caused by over-farming and overgrazing. The environmental costs do not end here.

On average, one pound of meat requires between 5,000 and 20,000 liters of water for direct and indirect use [6,10]. In the United States, 25 trillion liters of water are used for animal feed alone [10]. After everything is processed, researchers have found that in the U.S. 40 percent of freshwater is deemed unfit for drinking or recreational use due to contamination by microorganisms, fertilizers, and pesticides. For example, total phosphorus excretions of many livestock are seven to nine times greater than that of humans, resulting in disastrous effects to surrounding ecosystems. Furthermore, runoff from manure fosters an ideal environment for a number of waterborne pathogens. Case studies in China, India, the U.S., and Denmark indicate that “animal waste is a leading factor in pollution of land and water resources” [11]. Concentrated animal feeding operations (CAFOs) proliferate these issues as dense groups of livestock are raised in very confined conditions.

A report by the Food and Agriculture Organization of the United Nations estimates that livestock, including poultry, accounts for 14.5 percent of anthropogenic (human-induced) greenhouse gas emissions. About 44 percent of the emissions are from methane, 29 percent from nitrous oxide, and 27 percent from carbon dioxide. Methane is 28 to 36 times more effective than carbon dioxide in trapping heat and nitrous oxide is 265 to 298 times more effective than carbon dioxide [8,14]. Research led by the University of Oxford and University of Amsterdam found that producing beef consumed the greatest amount of energy, land, and water, and it emitted the greatest amount of greenhouse gases relative to sheep, pork, and poultry. Concern is rising as the population is expected to reach 9.6 billion by 2050, causing many to consider solutions that can help mitigate and prevent the effects of animal agriculture. One such emerging solution is cultured meat, otherwise known as in vitro meat.

 

Cultured Meat, Myogenesis, and Choosing the Most Applicable Stem Cell

Cultured meat, which goes by a variety of names — in vitro meat, synthetic meat, lab-grown meat — is meat that is grown from cell culture rather than a full-fledged animal. In Vitro Meat Production System (IMPS) utilizes the same protocol for tissue engineering techniques that are traditionally used in regenerative medicine. The first cultured burger made out of cow muscle was made by Mark Post in 2013 from Maastricht University in the Netherlands, with some modifications made since then. There are a number of ways to produce cultured meat such as the Self-organization technique, where muscle cells are maintained in vitro and nourished with the suitable nutrients, or the Scaffold-based technique, which utilizes stem cells that are allowed to be differentiated and grown into muscle tissue in vitro [19]. Initiating the Scaffold-based technique calls for the best possible stem cells to be utilized.

At first, embryonic stem cells may seem to be the most obvious choice for IMPS, since they provide virtually unlimited regenerative potential. However, genetic mutations have proven to limit the “production potential” of an embryonic stem cell [19]. Once stimulated, these cells do not necessarily retain the same proliferative characteristics; therefore, it has not been possible to culture cells with “infinite self-renewal capacity” [19]. The next option is myosatellite cells, also called satellite cells, which are found in muscle tissue that are repeatedly able to conduct the process of myogenesis, otherwise known as muscle generation, with “high efficacy.” Moreover, satellite cells have been proven to be integral because they “fulfill the criteria for a true somatic stem cell: self-renewal and the ability to generate progeny of several distinct cell types” [18,19].

 

Isolation and Proliferation of Satellite Cells

For the purposes of producing meat for edible consumption, researchers at various institutions have aimed to produce skeletal muscle. Satellite cells, which are found next to the muscle cells, are isolated from the animal following a biopsy [16,17]. In this step, a sample of skeletal muscle is collected from the organism and approximately 100 cells are isolated. Since these specific cells become activated in response to an injury or stress, they can be harnessed to grow muscle cells for consumption. Once isolated, proliferation can begin.

During proliferation, the goal is to produce as many satellite cells as possible in order to activate them to transition into myocytes or tubular muscle cells. A culture medium with the appropriate growth factor promotes the culturing of the stem cells. Generally, the medium is sourced from an adult, newborn, or foetus animal. The growth factor is made via muscle cells coupled with other cells types such as hepatocytes [18,19].

 

Differentiation, Fusion, Polishing, and the End Result

To enter differentiation, a change in medium is required to meet the changing demands of the new cells [17,19]. Unfortunately, the medium contributes to the high expenditure required towards overall costs as it requires regular replenishing from Fetal Calf Serum, which often raises ethical concerns. Many question the ethics as the serum is sourced from calves, and each calf can only produce a relatively small amount. Alternatives like sphingosine 1-phosphate and amino-acid rich mushroom extracts have been suggested for the serum-based media to replace the Fetal Calf Serum [19]. Over time the satellite cells will become myoblasts, otherwise called activated satellite cells. With continuous replenishment of serum the myoblasts differentiate into myscotytes. These long tubular cells form muscles.

An edible or non-edible non-animal-based scaffold is used to help the cells attach to a surface. Additionally, a scaffold that imitates tissue-like flexibility and stiffness will mimic in vivo conditions the best. As the cells are allowed to contract, further differentiation can occur [19]. Polymers like collagen or cellulose have been suggested as the basis for the scaffold since they may provide the most life-like circumstance. The myocytes fuse together to form myotubes, which eventually becomes a body of skeletal muscle. The cells need to be continuously allowed to contract in order to avoid atrophy, a condition of muscle wasting. Electrical stimulation coupled with the scaffold has been shown to be resourceful in some organisms [19].

For large-scale productions the usage of a bioreactor is necessary to provide the adequate conditions. Lastly, to provide a texture and flavor similar to traditional meat, Edelman et. al have suggested co-culturing myoblasts with fat cells [20]. However, other methods include mixing the meat with fat cells and additives to mimic farmed meat.

 

The Implications

Researchers from the University of Oxford and the University of Amsterdam have found a substantial decrease in negative environmental impacts from large-scale production of cultured meat in comparison to its traditional counterparts of beef, sheep, pork, and poultry meat. The production of 1000 kg of cultured meat requires 7 to 45 percent lower energy use than traditional meat, except for poultry, which requires less than cultured meat. The study shows 78 to 96 percent less greenhouse gas emissions, 99 percent less land use, and 82 to 96 percent less water usage with cultured meat. Variation in percentage points were attributed to the different organisms that cultured meat was compared to [15].

It is crucial to note that the protocols required to make cultured meat in IMPS require components from animals that still need to be farmed — for the time being. Acquisition of satellite cells require muscle samples, and the medium required to culture the cells, Fetal Calf Serum, shows that lab grown meat is not quite independent of traditional animal agriculture. However, with advancements in tissue engineering and improvements made to the techniques, it may be possible to bring cultured meat to market that no longer requires animal farming.

 

References

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