Cell Ag vs. Cell Therapy

Recent PhD graduate in Biochemical Engineering, Dr. Nuttinee Yongsanguanchai explains the similarities and explores the stigmas attached to cellular agriculture, cultivated meat, regenerative medicine and cell and gene therapy.

Over the past few years there has been lots of media coverage on plant-based proteins, cellular agriculture and cell-based meat, with multiple companies successfully producing products and proofs of concept.

When I attended New Harvest Conference in 2019 and presented my poster on my PhD research titled “The Combined Effects of Young’s Modulus and Low Oxygen Tension on Human Pluripotent Stem Cells,” 90 percent of my questions were “how do human stem cells have anything to do with the Cellular Agriculture industry?” Additionally, I often get comments from my peers in the biotech industry who don’t realize bioprocessing is used in both industries. The cell-based meat industry is often overlooked by the cell and gene industry, as to them it is seen as “inferior.” People deem it “inferior,” as it’s “not saving human lives.” Yet if you delve into the cellular agriculture industry, it is solving food security, mitigating greenhouse gases, deforestation, global warming and antibiotic resistance. Cell and gene therapy are the clinical applications treating illness and diseases — fairly similar.

Cell-based meat is the production of animal meat for consumption. Bioprocessing is the term used to describe the process of manufacturing these products. The main similarity between the two industries is that they share the same bioprocesses and require the same expertise. This article will briefly introduce the different industries and identify the more nuanced similarities between them.

Cellular agriculture is separated into two distinct fields. Firstly, cell-based meat, alternatively lab grown, cultured, or cultivated meat, is the term used to describe food products grown in the laboratory. A non-invasive cell sample is taken from the animal and the cells are multiplied and grown in a laboratory. There are a plethora of reasons why cell-based meat is a good alternative to conventional meat, including how it avoids slaughtering animals and reduces deforestation, global warming and antibiotic overuse (which leads to antibiotic resistance). Secondly, alternative proteins are food products that imitate meat, but are not made from animal cells. They are usually made from plant-based proteins such as soy proteins, mung bean protein and fungi. However, they still use similar bioprocessing techniques.

The definition of regenerative medicine is the “process of replacing, engineering or regenerating human or animal cells, tissue or organs to restore or establish normal function” (Mason and Dunnill, 2008). Cell and gene therapy is a part of regenerative medicine and is further divided into cell therapy and gene therapy. Gene therapy is therapy that involves anything to do with genetic material, whereas cell therapy is therapies using cells. They can be used in combination to first genetically modify a specific cell, which is then multiplied through a process known as culturing. An example of this is the CAR-T cell Therapy which involves the modification of a cancer patient’s own T-cells, a form of white-blood cell, multiplying them and then re-introducing the cells into the patient to battle the cancer.

Bioprocessing is a series of steps required to produce the product. Bioprocessing is usually divided into 2 main groups: upstream and downstream. Upstream involves the expansion and production of the product and downstream includes all the steps necessary for the purification of the product. The basic bioprocess usually found in the pharmaceutical industry for production of monoclonal antibodies, vaccines, cell and gene therapies are the same as the bioprocessing steps in food products such as beer, whiskey, plant-based proteins and cultured-meat production.

The upstream bioprocess is similar in all industries in the sense that they all need bioreactors in the expansion step, however, there are different types of bioreactors and different preparation steps. The downstream process may vary and can include centrifuges, homogenisers, chromatography, filtration and pasteurisation steps.

Common pharmaceutical products such as monoclonal antibodies and vaccines are different to cell and gene therapy, cultured-meat, beer and whisky products. As the products are usually intracellular (inside the cell, where the cell is broken), product is released into the solution media the cell is in. The difference to these products and cell and gene therapy, cell-based meat, beer and whisky products is that in this case, the products are the cells themselves.

Cell-based meat and cell and gene therapy both have the same upstream process as they both are culturing cells. There are 2 main types of cell cultures, adherent and suspension. Adherent cells are when the cells must be attached to a surface and suspension cells are cells grown in a liquid media. A good example would be corals grown on reefs for adherentand fish in the sea for suspension.

As these mammalian cells are adherent, they both face the same scaling up challenges. Cellular agriculture such as alternative protein and vaccine manufacturing are grown using suspension cells which are easy to scale up as to do so, they would just increase the bioreactor size. As adherent cells need to be attached to a surface, it is more difficult. This is a major challenge in the lab grown meat industry as the stem cells, muscle cells and fat cells are all adherent cells. Similarly, in cell and gene therapy, human embryonic stem cells, human induced pluripotent stem cells (which include mesenchymal stem cells), adipose stem cells, hematopoietic stem cells, neural stem cells and epithelial stem cells are all adherent cells. Therefore, both industries must explore methods on how to scale up when using adherent cells. Solutions include cell culturing chambers (flask with large surface area), microcarriers (beads in the media solution to provide surface for the cells to attach and grow on) and adapting the adherent cells into a suspension culture (which have been done in the pharmaceutical industry, for example, with the adaptation of Chinese hamster ovary (CHO) cells and Human Embryonic Kidney (HEK293) cells to a suspension culture).

Another similarity in cell culturing with these industries are that they both use the same nutritional supplements to feed the cells, known as media. Media is used for growth and maintenance of all cells as well as supplements which can be used for the differentiation of stem cells into specific cell types. A simple analogy is to think of how pigs, chickens or cows can all eat the same foods, such as corn.

Cell and gene therapy and cell-based meat are for human use and consumption and both face safety hurdles. For the cell and gene therapy industry, their aim is to replace cells in the body with healthy cells grown in the lab. In the cell-based meat industry, it is for human consumption. Both industries’ final products are to be used in the human body and both have goals of improving the human experience. Cell and gene therapies are regulated through the Food and Drug Administration (FDA), whereas agriculture is usually regulated by the United States Department of Agriculture (USDA). With this new cell-based meat, the USDA has partnered with the FDA to oversee the industry. Unlike the US, in Europe it would need approval by the European Food Safety Authority (EFSA), as it is within the Novel Foods Regulation.

In conclusion both these industries use the same equipment, products and protocols. The only difference is the human cells grown in the cell and gene therapy industry and the animal cells grown in cell-based meat. There are professionals in the Cell and Gene Therapy industry that sometimes think the cultured-meat industry is inferior to their own; however, not only does the cultured meat industry present climate solutions like the ones mentioned above, but the food market is expected to be over $4 Trillion by 2024 (IMARC Group, 2019) with the cultured-meat market expected to grow by $200 Million (Technavio, 2019). After all, everyone’s got to eat!

Written by Nuttinee Yongsanguanchai.

PhD in Biochemical Engineering and Regenerative Medicine, MSc in Biochemical Engineering and BSc in Nutrition and Food Science.

Reference

IMARC Group. (2019). Food Service Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2019-2024. IMARC Group Available at: https://rb.gy/khvvai (Accessed: 22 August 2020)

Mason, C. and Dunnill, P. (2008) A brief definition of regenerative medicine, Regenerative Medicine. doi: 10.2217/17460751.3.1.1.

Technavio. (2019). Cultured Meat Market by Product and Geography – Forecast and Analysis 2020-2024. Technavio. Available at: https://rb.gy/khvvai (Accessed: 20 August 2020)



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