Part 1: Types of Cells Used for Cultivated Meat
The goal of cultivated meat is to produce meat without the need for raising and slaughtering animals. To understand how this works, it’s important to first consider what conventional meat is made of. Conventional meat consists primarily of muscle cells, fat cells, and connective tissue cells.
- Muscle Cells create the meat's texture and serve as the primary mass in meat.
- Connective Tissue Cells contribute to the meat's texture and structure.
- Fat Cells are important for the taste, juiciness, and mouthfeel of meat.
The aim of cultivated meat production is to replicate these components by growing the necessary cells in a lab.
In cultivated meat production, the target cells to replicate are the muscle, fat, and connective tissue cells found in conventional meat. These cells are the end product of the cultivation process and are crucial for creating a product that looks, tastes, and feels like real meat. It’s important to note that different cell types (i.e., muscle, fat, and connective tissue) cannot be grown together at the same time in the same bioreactor. If the end product is to contain a mixture of these cells, the combination process is done later, not during the bioreactor stage.
Once you know the end product, you can determine the "starter cells" required as the source.
The Importance of Starting Cells
For cultivated meat production to work, regardless of the cell type you're trying to cultivate, you need "starter cells" with two critical properties: differentiation and proliferation.
- Differentiation is the process by which a young, unspecialized cell changes into a specialized cell with a specific role in the body. The muscle, fat, and connective tissue cells that we eat are specialized cells that have differentiated from young, unspecialized cells.
- Proliferation refers to the ability of these starter cells to divide and multiply, ensuring that there are enough cells to produce the desired amount of meat.
Introduction to Adult Stem Cells
One of the most common types of starter cells used in cultivated meat production is adult stem cells. These cells, found in adult tissues, can both proliferate and differentiate into specific cell types, such as muscle or fat cells. This makes them particularly well-suited for use in bioreactors, where they can be expanded and differentiated to produce the necessary muscle, fat, and connective tissue cells for meat production.
Types of Adult Stem Cells Used in Cultivated Meat
There are several types of adult stem cells used to produce cultivated meat, including Satellite Cells, FAPs, and MSCs. For simplicity, although FAPs are technically progenitor cells, we will group them with stem cells.
- Satellite Cells: Essential for producing muscle fibers, making them highly valued for replicating the texture and structure of conventional meat.
- Fibro-Adipogenic Progenitors (FAPs): Can differentiate into both adipocytes (fat cells) and fibroblasts (connective tissue cells). This dual potential is valuable for cultivated meat production, as they contribute to both the muscle and fat components, enhancing flavor and texture.
- Mesenchymal Stem Cells (MSCs): Versatile cells that can differentiate into multiple cell types, including muscle and fat cells. Their flexibility and ease of isolation make them an excellent option for creating various components of meat products.
Obtaining Adult Stem Cells from Animals
To obtain these adult stem cells, cultivated meat producers typically start by taking a small tissue sample from the animal. This sample is usually taken from a live animal, which remains alive after the biopsy, though it may sometimes come from the carcass of a recently slaughtered animal. Once collected, the specific adult stem cells of interest—such as satellite cells, FAPs, or MSCs—are isolated and prepared for further use in the production process.
Challenges with Direct Extraction
While directly extracting adult stem cells from animals is effective, it does present certain challenges, including the limited proliferative capacity of the cells (meaning they can only divide a certain number of times) and the invasive nature of the biopsy. Additionally, variability in cell quality from one animal to another can pose a challenge for consistent production.
Alternative Approaches: Pluripotent Stem Cells
To overcome these challenges, cultivated meat producers can turn to alternative approaches involving pluripotent stem cells. Pluripotent stem cells have the ability to proliferate indefinitely, offering a more sustainable and scalable option. Unlike adult stem cells, which are specialized and can only become specific types of cells, pluripotent stem cells can differentiate into any cell type, including muscle, fat, and connective tissue cells. This versatility makes them extremely useful for creating different components of meat.
The Journey from Embryonic Pluripotent Stem Cells to Adult Stem Cells
To appreciate the role of pluripotent stem cells in cultivated meat production, it's essential to understand their place in the natural developmental hierarchy of cells. Embryonic Pluripotent Stem Cells (ESCs) are foundational cells present during the early stages of embryonic development. These cells come from the inner part of a tiny group of cells (the embryo) that forms just a few days after fertilization. Their defining characteristic is the ability to differentiate into any cell type in the body. As the embryo develops, these ESCs give rise to various adult stem cells, which reside in specific tissues, serving as reservoirs for cell regeneration and repair. For instance, satellite cells, the adult stem cells found in muscle tissue, originate from these embryonic pluripotent cells.
In cultivated meat production, leveraging pluripotent stem cells means tapping into this natural developmental pathway at an earlier stage. This approach allows producers to mimic the body's intrinsic processes, guiding pluripotent cells to become adult stem cells and, subsequently, the specialized cells needed for meat production.
Integrating Pluripotent Stem Cells into the Cultivated Meat Process
When pluripotent stem cells are used as the starting point in cultivated meat production, the process involves an additional step of cellular differentiation. Instead of directly expanding adult stem cells to produce specialized meat cells (adult stem cell → specialized adult cell), the sequence unfolds as follows: pluripotent stem cell → adult stem cell → specialized adult cell. Essentially, you are sourcing the starter cell at an earlier stage.
Initially, pluripotent stem cells are directed to differentiate into specific adult stem cells, such as satellite cells for muscle or mesenchymal stem cells for fat and connective tissue. Once these adult stem cells are established, they undergo proliferation and further differentiation to become the mature cells that compose the meat.
While this method introduces an extra step, it offers significant advantages. Pluripotent stem cells can proliferate almost indefinitely and can be coaxed into becoming any desired cell type, providing a flexible and scalable foundation for cultivated meat production.
Obtaining Embryonic Stem Cells (ESCs) for Cultivated Meat
As mentioned earlier, ESCs are derived from an early-stage embryo formed a few days post-fertilization. In cultivated meat production, obtaining ESCs involves creating these blastocysts through in vitro fertilization (IVF) techniques. Sperm and egg cells from the target animal are combined in a controlled laboratory setting, leading to the formation of an early-stage embryo. The ESCs are then harvested from this embryo.
Generating Induced Pluripotent Stem Cells (iPSCs) for Cultivated Meat
The process of obtaining ESCs can be expensive, especially when trying to make cultivated meat a commercially viable endeavor. An alternative is to use a different kind of pluripotent stem cell called Induced Pluripotent Stem Cells (iPSCs). iPSCs are created by reprogramming adult cells—such as skin or blood cells—back into a pluripotent state. This process is like taking a fully specialized cell and reversing it back to an earlier stage, where it behaves like a stem cell with the ability to develop into any cell type.
ESCs vs. iPSCs: Similarities and Differences
Both ESCs and iPSCs are types of pluripotent stem cells, sharing key characteristics:
- Differentiation Potential: Both can differentiate into any type of adult stem cell, which then becomes specialized adult cells, such as muscle or fat cells.
- Proliferation Capacity: Both can renew indefinitely, providing a consistent and scalable source of cells.
The key difference between the two is that ESCs occur naturally, while iPSCs are created through genetic modification.
Differentiating Pluripotent Stem Cells into Adult Stem Cells
When using pluripotent stem cells (PSCs) as the starting point for cultivated meat production, it’s essential to recognize that there is an additional step compared to starting directly with adult stem cells. This extra step involves guiding the PSCs to first differentiate into specific adult stem cells, such as satellite cells or mesenchymal stem cells. Only after this step can they then proceed to differentiate into the final, specialized cells that make up the cultivated meat product.
Other Considerations for Source Cell Selection
In addition to choosing the type of cell to start with, several other factors must be considered in the selection process:
- Species of Animal: The species from which the cells are sourced is crucial, as it determines the type of meat being produced.
- Health of the Source Animal: Ensuring that the animal from which the cells are taken is healthy is important for the quality of the final product.
- Ethical and Branding Considerations: How the cells or biopsy are taken from the animal can impact the brand's image.
- Biopsy Location: If the source cells are adult stem cells extracted from a biopsy, the location of that biopsy can affect the properties of the adult cells and, subsequently, the taste and texture of the meat.
Part 2: What Is a Cell Line and Why Is It Relevant to Cultivated Meat Production?
The current goal and challenge in cultivated meat production is not just about how to do it but how to do it at scale and make it financially feasible. It’s not practical or cost-effective to continuously obtain source cells from the target animal (or, in the case of ESCs, to create a new early-stage embryo) every time you want to produce a batch of cultivated meat. This is where the concept of cell lines comes in. Cell lines provide a stable and renewable source of cells that can be continuously expanded and used across multiple production cycles. It’s like making copies of a popular book in a library—once you have the original, you can keep making copies without needing to rewrite the entire book each time.
What Is a Cell Line?
A cell line is a population of cells grown in a laboratory that originates from a single cell. There are various stages of cell line development, starting with the initial batch of source cells, known as the Primary Source Cells or Primary Cell Culture.
This batch of Primary Source Cells (whether ESCs, iPSCs, or adult stem cells) is then made to multiply in number, establishing what is known as the Primary Cell Line.
The cells within this Primary Cell Line are further multiplied through a process called subculturing, where the cell batch is gradually transferred into larger containers to allow for further expansion.
Once this subcultured cell line population is large enough, the lab reviews the batch and selects the best cells for production. This stage, known as Cell Selection, is where a stable cell line is established. This stable culture of cells can consistently multiply and maintain the desired conditions.
These stable cell lines are then used in the bioreactor process, where they further grow and differentiate into meat cells. If the cultivated meat producer has opted to use a pluripotent cell as their starter cell (i.e., ESC or iPSC), then the stable cell line will also be a batch of pluripotent stem cells. In this situation, the stable cell line undergoes an additional process of differentiation into an adult stem cell as part of the bioreactor preparation/production process.
Each time a cultivated meat company wants to produce a batch of meat, they don’t have to go through the process of culturing and sorting the source cells first. They can start the process with a pre-cultured and consistent supply of starter cells.
Part 3: Challenges in Choosing and Developing Cell Sources for Cultivated Meat
One of the biggest challenges in cultivated meat production is figuring out how to do it in a way that can be scaled up to meet demand and keep costs down. A key part of this challenge is deciding what type of cells to use and how to develop cell lines that can be grown repeatedly without starting from scratch every time.
Choosing the Right Type of Cell
The first challenge is choosing which type of cell to start with. Producers have to decide between using adult stem cells or pluripotent stem cells, each with its own pros and cons:
- Mature Cells: Easy and cheap to obtain but can only grow and multiply a limited number of times.
- Adult Stem Cells: Can multiply better and are easier to obtain from animals, but they still have limits on how much they can grow.
- Pluripotent Stem Cells: Can grow indefinitely and become any type of cell needed for meat, but they are more difficult and costly to work with.
The Challenges of Using Pluripotent Stem Cells
Pluripotent stem cells, like ESCs and iPSCs, offer the advantage of being able to turn into any type of cell and can grow continuously. However, using these cells isn’t straightforward. ESCs are difficult to obtain because they come from embryos at a very early stage, raising ethical concerns. iPSCs are created by reprogramming regular cells, like skin or blood cells, to act like stem cells. While reprogramming is well-developed for human cells, doing this for animal cells used in meat production is still a work in progress and requires more research.
Even though pluripotent stem cells are versatile, they take more time and resources to turn into the specific cells needed for meat compared to adult stem cells, which are already partway there. While these cells can be a powerful option, they require careful handling and are more resource-intensive.
Balancing Growth and Specialization
Another important consideration is balancing how well the cells can grow with how easily they can become the specific muscle, fat, or other types of cells needed for meat. It’s not enough for the cells to grow rapidly—they also need to reliably turn into the right kinds of cells that make the meat taste and feel like the real thing. Finding this balance is key to producing cultivated meat efficiently and at a high quality.
Ensuring Cell Line Suitability and Stability
Creating a dependable cell line isn’t just about finding cells that can keep growing. The cells also need to be suitable for producing meat with good taste, texture, and nutrition. Not all cell lines behave the same way—some might grow well but fail to make good meat. Additionally, these cell lines need to remain consistent over time, producing the same results without unexpected changes. Maintaining this consistency can be tricky because even small changes in the cells can lead to problems with the final product.
Regulatory and Market Barriers
Meeting regulatory standards is another challenge. Cell lines used for cultivated meat must be proven safe for consumption, and obtaining this approval can be time-consuming and costly. Moreover, there aren’t many suppliers offering high-quality cell lines for meat production. Most suppliers focus on human or mouse cells, which are not directly relevant for food production. This shortage makes it difficult for companies to access the right cells for large-scale production.
Structuring the Final Product
The type of cells chosen can also affect the structure of the final meat product. For simpler products like minced meat, it’s easier to focus on growing cells quickly and in large amounts. However, creating more complex products like steaks or fillets requires cells that can be organized into layers or structures that mimic real meat. This adds another layer of difficulty when choosing and developing the right cell sources.
Part 4: What Is Cell Banking for Cultivated Meat?
Cell Banking
Most people are familiar with the concept of a sperm bank, where sperm is stored for future use. A cell bank operates similarly. Once a stable cell line has been established—a stable population of cells that can be reliably used for cultivated meat production—this cell line is frozen and preserved so that producers can access it in the future on demand. This process of freezing and preserving the cells is called cell banking.
The Cell Banking Process
During cell line development, a stable population of cells is selected, established, and optimized for characteristics like growth rate, differentiation potential, and stability. The result is a well-characterized and reproducible cell line that serves as the foundation for large-scale meat production.
Once this optimal culture of cells has been established, it is expanded in a bioreactor to create many vials containing copies of these cells. These are frozen and stored, forming the Master Cell Bank (MCB).
A single vial from the MCB is then further expanded to create a secondary batch of vials containing these cells. These are also frozen and stored, forming the Working Cell Bank (WCB). Cultivated meat producers use cells from the WCB for regular production needs.
During the cell banking process, rigorous testing ensures that the stored cells remain safe, stable, and consistent over time. This includes checks for cell viability (to confirm they survive freezing and thawing), contamination (to ensure they are free from bacteria, fungi, and other unwanted organisms), and genetic stability (to verify the cells don’t undergo unwanted changes). While similar tests are done during cell line development, these focus on establishing a stable and reliable cell line in the first place. In contrast, cell banking testing is more about confirming that the cells maintain their quality during long-term storage and can be used consistently across multiple production cycles. The goal is to ensure that the cells behave predictably every time they’re used, even after being stored for extended periods.
The Two-Tiered MCB-WCB System
The two-tiered MCB-WCB system is key for ensuring that the cells used in cultivated meat are consistent, safe, and easy to scale up. The Master Cell Bank (MCB) is the original, carefully tested batch of cells stored long-term. From this, multiple Working Cell Banks (WCBs) are created, which are used in day-to-day production. This setup keeps the original cells safe while providing a steady and reliable supply of cells that behave consistently every time they’re used. The system also reduces risks like contamination and changes in cell quality over time. Additionally, it helps meet regulatory standards by ensuring the cells are well-documented, safe, and traceable—crucial for producing meat on a large scale.
The Cell Banking Market: Key Players and Options for Cultivated Meat Producers
The cell banking market is a well-established industry that primarily serves biotechnology, pharmaceuticals, and research sectors. It includes companies specializing in creating, storing, and supplying cell banks for various applications. Major players in the cell banking industry include ATCC, Thermo Fisher Scientific, and Kerafast. These suppliers offer a wide range of cell lines, from human and animal cells to microbial cultures, many of which are used in research, drug development, and biomanufacturing.
However, the options available for cultivated meat producers are more limited. Most traditional cell banking companies focus on human and mouse cell lines, which are not directly relevant for food production. As a result, cultivated meat companies either need to develop their own specialized cell banks for species like cattle, chicken, or fish, or rely on emerging companies and research institutions that are working on developing and supplying cell lines specifically for cultivated meat. Some cultivated meat producers also partner with specialized biotech firms that focus on developing cell lines tailored for food applications, such as Good Meat and Aleph Farms.
Options Available to Cultivated Meat Companies
Cultivated meat companies have several routes they can take when sourcing and banking their cells:
- Developing In-House Cell Banks: Some companies choose to establish their own cell banks from scratch. This involves sourcing the original cells (e.g., through a biopsy from the target animal), developing a stable cell line through testing and selection, and then creating their own master and working cell banks. This approach gives producers full control over the entire process, from the original cell source to production.
- Partnering with Cell Line Developers: Some companies collaborate with specialized biotech firms that focus on developing cell lines optimized for food production. These partners handle the development and initial banking of the cell lines, allowing cultivated meat companies to focus more on scaling up and production.
- Purchasing Ready-Made Cell Lines: As the cultivated meat industry grows, there are emerging suppliers focusing specifically on providing ready-to-use cell lines for meat production. These suppliers offer pre-developed cell lines that are already tested and optimized for producing muscle, fat, or connective tissue cells, saving producers time and resources.
Difference Between a Cell Banking Company and a Cultivated Meat Producer
It’s important to understand the distinction between cell banking companies and cultivated meat producers.
- Cell Banking Companies are specialized businesses that focus on preserving, storing, and supplying cell lines. Their main role is to ensure that cell lines remain stable and viable over long periods and can be provided to companies whenever needed. They often provide cell banking services to a wide range of industries, from pharmaceuticals to research labs, and may not be involved in the actual production of cultivated meat.
- Cultivated Meat Producers are companies whose primary focus is on creating meat products using cell culture technology. While they rely heavily on stable cell lines, their expertise and resources are more focused on growing, differentiating, and harvesting these cells in bioreactors to produce meat at scale. While some cultivated meat companies develop and bank their own cell lines in-house, their main objective is not cell banking itself, but rather the large-scale production of meat.
Summary
The cell banking market, while mature in other industries, is still developing when it comes to cultivated meat. Traditional suppliers like ATCC and Thermo Fisher offer limited options for food-relevant cell lines, pushing many cultivated meat companies to either develop their own cell banks or partner with specialized biotech firms. Whether building in-house or sourcing externally, having a reliable cell bank is crucial for cultivated meat producers as it provides the foundation for scalable and consistent meat production. The distinction between cell banking companies and cultivated meat producers lies in their focus: cell banking companies preserve and supply cells, while cultivated meat producers focus on using those cells to create food products.