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Published October 23rd, 2023

Unlocking cultivated meat's potential with stem cell lines

Cultivated meat production is on the rise, and one of the key requirements is finding the optimal starting cell source. To achieve this, stem cells are the strongest candidate for the job. Adult stem cells and pluripotent stem cells possess the necessary abilities to self-renew and differentiate into mature cell types.

Join us as we explore the exciting world of stem cell lines for cultivated meat production. We'll delve into the key characteristics of an optimal stem cell line, existing cell sources, and the challenges we still need to overcome to achieve scalability.

Through this exploration, we aim to provide insights into the current state and future of cultivated meat production. We hope you find it an informative and engaging read!

What is a stem cell?

Stem cells are cells that have the unique ability to differentiate into various animal cell types, such as muscle cells, fat cells, or blood cells. They can also self-renew, meaning they can divide and make more copies of themselves, which makes them incredibly useful for many different types of medical research and treatments, as well as for the alternative protein industry.

Stem cells can be found in embryos and fetal tissue. They are also present in small numbers in various tissues and organs throughout the body (known as adult stem cells), such as bone marrow, skin, and brain.

Adult stem cells are found in various animal tissues and organs, such as the skin and bone marrow of cows

In their natural environment, stem cells derived from embryonic and fetal tissue are essential for the normal development of a fetus. Adult stem cells are involved in tissue regeneration and help to replace cells that have been lost due to everyday wear and tear, injury, or disease.

In a lab environment, culturing stem cells under specific conditions can encourage them to divide and differentiate into all sorts of mature meat cells, which can then be used to create a variety of meat products.

Establishing stem cell lines for cultivated meat

Cultivated meat requires large quantities of different animal cell types to be grown in a controlled environment, which makes stem cells an ideal source for scaling up production. But to ensure a consistent and sustainable source of cells, one must first establish a stable stem cell line, meaning a population of stem cells that can divide and multiply indefinitely.

To establish stem cell lines for cultivated meat, stem cells need to be isolated from an animal source and maintained so that they can grow in a lab indefinitely. Growth factors and nutrients can subsequently be used to induce the stem cells to develop into different cell types.

The characteristics of an optimal stem cell line

An optimal stem cell line for cultivated meat should demonstrate several characteristics:

1. Appropriate potency

Stem cells have varying degrees of potency; in other words, the ability to differentiate into various cell types. Since we require specific cells to create lab-grown meat products, it’s important to source a stem cell line that can differentiate into the cell types that make up meat tissue, such as skeletal muscle cells, adipocytes, and fibroblasts.

Pluripotent stem cells, which are commonly used in cultivated meat production, can differentiate into cells from all three germ layers (primary layers of cells that form during embryonic development, which give rise to the different tissues and organs in animals), including the cell types that make up muscle tissue. There are two types of pluripotent stem cells: embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).

iPSCs are reprogrammed primary cell types, which have been returned to a pluripotent state

Adult stem cells, also referred to as multipotent, have a more restricted ability to differentiate compared to pluripotent stem cells. They can only transform into multiple cell types that belong to the same germ layer as the tissue from which they originated. The pros and cons of using pluripotent as opposed to multipotent stem cells will be discussed below.

2. Self-renewing

The ability of stem cells to self-renew is essential for the production of cultivated meat because it allows for the production of large quantities of cells from a small starting population. Without this ability, it would be necessary to continually obtain new cells from an animal, which would be expensive, time-consuming, and may require the continuation of unethical practices.

When stem cells divide, they can produce either two identical stem cells or one stem cell and one differentiated cell. Stem cells that are able to divide indefinitely while maintaining their undifferentiated state are said to have self-renewal capacity. This allows a small number of starting stem cells to be expanded into a large population of cells for use in cultivated meat production.

For example, to produce a single breast of lab-grown chicken, millions of cells are needed, and this number increases exponentially as the production scale is increased. A stem cell line with a high self-renewal capacity can provide the large number of cells required for cultivated meat production.

3. Genetically stable

When cells replicate, their DNA is also duplicated, and errors can occur during this process, leading to genetic mutations that can affect the quality and safety of the meat produced. Genetic instability can cause unintended changes in the cells' characteristics and properties, leading to inconsistent results in the meat's texture, flavor, and nutritional content. Therefore, a genetically stable stem cell line is crucial to ensure the consistency and safety of the cultivated meat product.

Additionally, ensuring genetic stability is important for regulatory compliance and maintaining consumer confidence in the safety and quality of the product.

4. Scalable

Finally, stem cell lines should be scalable, meaning they can be rapidly expanded to produce large quantities of cells for commercial production. If a stem cell is not viable for scalability, it would be challenging to meet the demand for cultivated meat and could limit the potential for this technology to become a viable alternative to traditional animal agriculture.

In addition to the aforementioned traits, resilience to environmental variations and process fluctuations, compatibility with cryopreservation, cost-effectiveness, and rapid proliferation rates are all key factors influencing the scalability of a stem cell line.

Existing cell sources for cultivated meat production

90% of the meat we consume is made up of muscle fibers. The remaining 10% is a combination of fat, connective tissue, and blood. When we break these components down further, the primary cell type is skeletal myocytes, with fibroblasts, adipocytes, chondrocytes, and hematopoietic cell types playing integral supporting roles.

Meat is composed of a complex network of different cell types, with skeletal myocytes being the predominant cell type

There are three main cell sources that possess the necessary capacity to produce these cell types: pluripotent stem cells, adult stem cells (multipotent), and primary cell types.

1. Pluripotent stem cell lines

In addition to having the ability to differentiate into any animal cell type, pluripotent stem cells (including ESCs and iPSCs) can theoretically self-renew indefinitely under optimal conditions.

However, embryonic stem cells are obtained from the inner cell mass of a blastocyst, which is a structure that forms a few days after fertilization of an egg. This naturally raises ethical concerns since it requires the destruction of the embryo. Additionally, obtaining, stabilizing, and culturing pluripotent stem cells can be more technically challenging and expensive. As a case in point, embryonic stem cell lines for agriculturally-valuable bovine species were only successfully derived in 2018.

iPSCs, on the other hand, are generated by reprogramming primary cell types, such as skin or blood cells, back into a pluripotent state (typically via viral-mediated genetic modification). They share many characteristics with embryonic stem cells and offer the advantage of mitigating some of the ethical, technical, and financial issues regarding cell sourcing.

However, reprogramming can increase the risk of genetic abnormalities; companies should carefully consider the risks and benefits of using such methods and ensure that they comply with any relevant regulations. In addition, companies may choose to explore alternative reprogramming technologies that avoid genetic modification.

2. Multipotent stem cell lines (adult stem cells)

Adult stem cells are generally considered to be more ethically and easily obtained than pluripotent stem cells since they can be harvested from a variety of sources, such as muscle tissue or fat tissue, with minimal harm to the donor animal.

Muscle tissue has two main types of stem cells that can develop into the mature meat cells required for the production of cultivated meat, including:

Mesenchymal stem cells

Mesenchymal stem cells (MSCs), otherwise known as stromal cells, are a type of adult stem cell that can be obtained from numerous sources, including bone marrow, adipose tissue, umbilical cord, dental pulp, and placenta. Their multipotent nature means that they can be used to produce several principal mature meat cell types, including osteoblasts (bone cells), adipocytes (fat cells), chondrocytes (cartilage cells), and myocytes (skeletal muscle cells). However, their ability to differentiate into the latter may be restricted and influenced by the source of tissue.

Mesenchymal stem cells can be obtained using minor procedures such as an adipose tissue biopsy

Myosatellite stem cells

Myosatellite cells are a type of adult stem cell found in skeletal muscle tissue, responsible for muscle growth and repair. They hold significant potential as a cell source for cultivated meat production because they are among the most prolific tissue-specific stem cells in the body.

A minor tissue biopsy is all that is required to obtain myosatellite cells, which can be performed under local anesthesia. MSCs are the preferred adult stem cell type for obtaining and culturing skeletal muscle tissue in vitro but further research is needed to support their growth outside of their natural muscle environment.

3. Primary cell types

In addition to stem cells, it’s also possible to use primary cell lines to produce cultivated meat. Obtained from specific organs or tissues, primary cell types are better suited to more specialty ingredients, such as foie gras, since they have a finite lifespan for differentiation.

Nevertheless, an advantage of using primary cell lines is that they can be directly converted into desired cell types, which mitigates the complexities of maintaining stem cells in a pluripotent state. For example, reprogramming techniques have been employed to turn fibroblasts into skeletal muscle progenitor cells.

The future of stem cell lines

Stem cells have the unique ability to self-renew and differentiate into various animal cell types, making them ideal for producing large quantities of cells needed for meat production. Therefore, establishing stable and reproducible stem cell lines is essential for the continued growth of the cultivated meat industry.

An optimal stem cell line for cultivated meat should be self-renewing, genetically stable, scalable, and demonstrate appropriate potency. Existing cell sources include embryonic stem cells, induced pluripotent stem cells, adult stem cells, and primary cell types, each of which has distinct advantages and disadvantages.

Nevertheless, significantly more research is required to increase the amount of publicly available cell lines isolated from agriculturally-relevant species for cultivated meat production, the current lack of which highlights the need for the creation of biorepositories. This is partly being addressed by the Good Food Institute's "Frozen Farmyard" project in partnership with Kerafast.

The availability of diverse cell lines will be crucial in advancing research for the cultivated meat industry.

Want to learn more about stem cell lines?

We can help you achieve clarity regarding the entire value chain for cultivated meat products, from specific support in establishing stem cell lines and cultivating subsequent mature meat cell types to navigating complex food regulations and developing your go-to-market strategy. Get in touch with Bright Green Partners today.

Ready to discover what alt protein strategies could mean for your business? Discuss it in a 30 minute call with our Managing Partner, Floor.
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