All Things Stem Cell

On August 5, 2013, a “lab-grown,” 5-ounce burger patty was taste tested in London, U.K. The patty had been grown from muscle stem cells that were isolated from cows. While this piece of “meat,” which was said to have tasted “close to meat,” represents significant progress in the field of making lab-grown food, the current approach needs to be improved before widespread use is feasible; the patty cost over $330,000 to make (not to mention probably significant culturing time in the lab to generate the 20,000 muscle strands used to make the patty). Luckily, there are many avenues that can be explored to optimize this technology. To understand them, it’s important to first understand the muscle stem cells themselves and how they’re cultured.

Origins of Muscle Stem Cells:
During development, the embryo has three different tissue types that, together with the germ cells, will make up the animal’s entire body. These are called the three germ layers. One of these tissue types, specifically the mesoderm, develops into skeletal muscle cells (along with other cell types, including cardiac muscle, kidney cells, red blood cells, and smooth muscle). Some stem cells that have been isolated from muscle appear to be mesenchymal stem cells. Mesenchymal stem cells (MSCs) got their name because they’re thought to primarily contain progenitors in the mesenchyme, which is a collection of cells mostly derived from mesoderm. (The majority of these cells later make up supportive structures throughout the body, such as bone, cartilage, connective tissue, muscle, adipose tissue, and the lymphatic and hematopoietic systems.) MSCs are typically multipotent, which means they can differentiate, or turn into, multiple different cell types. Specifically, MSCs are usually confirmed to be MSCs by showing that they can differentiate into three different, standard mesenchymal cell types: osteocytes (bone), chondrocytes (cartilage), and adipocytes (fat).

In muscle, there are two main groups of stem cells: satellite cells and muscle-derived stem cells (MDSCs) (Jankowski et al., 2002). Satellite cells were discovered decades ago (Mauro, 1961) and are commonly simply (and perhaps confusingly) referred to as muscle stem cells. It’s thought that these cells can regenerate damaged skeletal muscle and self-renew, but their ability to differentiate is rather limited; they can only make other types of muscle cells. (They’re basically unipotent.) MDSCs, on the other hand, are thought to be a type of multipotent mesenchymal stem cell and possibly a precursor of the satellite cells. But not only can the MDSCs differentiate into mesenchymal cell types, they have been found capable of becoming non-mesenchymal cell types as well. However, when picking the right stem cells to use for making lab-grown meat, the ability to differentiate into many different cell types is, for once, not an appealing trait.

For making lab-grown meat, what’s needed the most is the muscle cells themselves. This is likely why Mark J. Post, the creator of the lab-grown patty (at the Cardiovascular Research Institute, Maastricht University, The Netherlands), recommended satellite cells as the “first and foremost” cells to use for these endeavors in a 2012 review on the subject (Post, 2012). The satellite cells, once they have enough numbers in a culture, can easily be turned into the different, desired muscle cell types, and not other, unwanted cell types, such as bone or cartilage. (It’s thought that there may even be more desirable subsets of these stem cells in muscle that researchers have yet to develop efficient isolation techniques for.)

Other Stem Cell Sources:
It’s possible that other types of stem cells could be used instead of these satellite cells, and including some may even be advantageous for improving the taste and texture of the lab-grown patty. Many different types of stem cells can turn into muscle, including all MSCs. Some potentially easy sources of MSCs include adipose tissue, umbilical chord tissue, and the circulatory system. Additionally, many different types of cells can be turned into muscle through a technique called direct reprogramming by exposing the cells to a transcription factor that’s naturally important for the identity of muscle cells (called MyoD). (Not to mention, it’s thought that any cell type can be turned into induced pluripotent stem cells, which, like embryonic stem cells, are pluripotent, meaning they can be differentiated into virtually any cell type, including muscle.) So, other cell sources could likely be used to make desirable muscle cells, but, depending on the cells, the differentiation process may be less efficient than just using satellite cells.

That said, because the taste testing of the lab-grown patty revealed that it may be lacking a fattiness that’s associated with normal beef patties, including some adipose (fat) cells in the mixture may be ideal, which Post himself suggested (Post, 2012). As mentioned earlier, MSCs can become fat cells, so there are many different tissue sources to choose from for including some fat. Or adipose-derived stem cells themselves could be isolated and used.

Cell Culture Hurdles and the Pursuit of Xeno-Free Culture:
While satellite cells can be harmlessly collected from cows, the process of growing and expanding those cells may require many additional animal products, some of which may make the end product costly and one that’s not widely accepted by vegetarians. For example, fetal bovine serum (FBS) is commonly used in cell media. It’s expensive and requires slaughtering animals, costing around $250 and up to three cow fetuses for each liter (Brindley et al., 2012). Post himself discussed that serum replacements are being explored (Post, 2012), but it’s hard to replace the “real thing;” we don’t understand all of the needs of these cells, and it’s easier to include a mixture of animal proteins than figure out which ones are vital and which aren’t. The best alternative may be to have bacteria synthetically make the key components so that animal-derived products, which can vary considerably from lot to lot, are less depended upon for the meat-growing process.

While the field of growing cells in an environment without animal-derived products (known as xeno-free culture) is a challenging one, it’s definitely been receiving more attention in recent years, mainly for transitioning stem cell technologies to clinical trials (since animal products should ideally not be included in stem cell-based therapies for humans). Perhaps xeno-free culture may lead to a more affordable lab-grown burger that, at the same time, is also more widely accepted by vegetarians.

References:

Brindley, D. A., et al. Peak serum: implications of serum supply for cell therapy manufacturing. Regenerative Medicine. 2012. 7(1): 7-13. View Article

Jankowski, R. J., Deasy, B. M., and Huard, J. Muscle-derived stem cells. Gene Therapy. 2002. 9(10): 642-647. View Article

Kitamura, M. Brin’s $332,000 Lab-Grown Burger Has Cake-Like Texture. Bloomberg. 2013, August 5. View Article

Mauro, A. Satellite cell of skeletal muscle fibers. The Rockefeller Institute, Brief Notes. 1961. View Article

Post, M. J. Cultured meat from stem cells: Challenges and prospects. Meat Science. 2012. 92: 297-301. View Article

Rowland, T. Lab-grown meat: Triumphs and challenges. Biology Bytes. 2013, August 8. View Article

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