Steakholder Meets: Diving into large scale growth

Orit:

Hello everyone and thank you for joining us, we will start shortly. Let’s wait a few seconds to let people join in. Idan, are you with me?  Great so let’s start!

Welcome to Steakholder Meets, the bi-weekly Twitter Space show brought to you by Steakholder Foods!

My Name is Orit Goldman, the VP of Biology, and I will be hosting Steakholder Meets. In today’s episode, I am excited to have Idan Lankri, my colleague and a researcher in Steakholder Foods.

After our previous episodes where we talked about the cell, the source, the isolation, the growth, the characterization, and our challenges, the process from an isolated cell to a cell line, today we’ll discuss the following process – the growth and suspension. So, if you’re curious about the scientific side of this exciting topic, stay tuned with us! If you are joining us live, drop your questions as comments on our Q&A tweet. We will leave some time for Q&A at the end of the show to answer any questions you may have.

Idan,  welcome! I am excited to have you here today.

Idan:

Thank you, I’m excited too.

Orit:
First, maybe we can start with a quick introduction.

Can you present yourself, and let us know why you decided to join Steakholder Foods?

Idan:

Hi, I’m Idan, I’m a bioprocess engineer, I’m responsible for the field of cells growth in bioreactors in general and suspension growth in particular at Steakholder foods, I have over 4 years of experience in the field of animal cells growth in bioreactors. And I came to Steakholder Foods because I think it’s a very important company that used cells from animals and have sustainable meat and it’s great.

Orit:

And we are grateful that you joined us.

Idan:

Thank you!

Orit:

So today we are going to talk about how to produce a large quantity of meat and for that we really need to understand what the cells need to do and how we need to culture them.

Idan can you please explain us what is cell growth in suspension? And why do we need it?

Idan:

First, we will explain the main methods of growing cells in the world of biology and biotechnology, namely growing cells in 2D and growing cells in suspension.

The choice between growing cells in suspension or growing cells in 2D, largely depends on the specific research or industrial application, and each method has its advantages and disadvantages.

So growing cells in 2D is more commonly used in cell culture research, as it allows for easy observation and manipulation of the cells. 2D cell culture is frequently used in basic research areas, such as cell biology and molecular biology, and also in applied areas, such as drug discovery and toxicity testing.

On the other hand, growing cells in suspension is more commonly used in industrial bioprocessing applications, where large quantities of cells are required for the production of biologics, such as monoclonal antibodies, vaccines, and recombinant proteins. Suspension culture is also used in tissue engineering, and stem cell research.

And now, in the recent years, suspension growth has become very common in the cultured meat industries

The process of cell growth in suspension is crucial to the production of cultured meat. So what is cultured meat? It’s also known as cell-based meat, is produced by taking a small sample of animal cells and growing them in a nutrient-rich solution, typically in bioreactors.

So, to achieve optimal growth and differentiation of the cells, they must be grown in suspension, which means that they are suspended in the nutrient-rich solution rather than being attached to a solid surface. This allows the cells to grow and divide freely, increasing their numbers and producing the desired tissue.

The process of cell growth in suspension for cultured meat production is similar to that used in other biotechnology applications, such as the production of biologics and pharmaceuticals. However, the specific conditions and nutrient requirements for culturing meat cells are unique and require specialized expertise.

Overall, the ability to grow animal cells in suspension is a key factor in the development of cultured meat as a sustainable and ethical alternative to traditional animal agriculture.

Orit:

So just to explain to people what a bioreactor is, it can start from 1 litter to 1000 litter. Right Idan?

Idan:

Exactly, yes.

Orit:

We understood that if we want to grow a large quantity of cells we need to  grow them in suspension. It is like when you want to fill a room with as much as you can of people you will need to fill all the volume of the room.

You said that usually cells in the lab are growing in 2D structure. How you manage to make them growing in suspension?

Idan:

There are several ways to carry out the adaptation process.

The first and the long way is to transfer a cell culture grown in 2D to a suspension growth.

The culture undergo a process of gradual adjustment to the new conditions. We start with a low density culture: To initiate the adaptation process, cells are first seeded at low density in suspension culture. This allows cells to adjust to the new culture conditions while minimal stress and competition. In addition, we use very low shear forces and dedicated tools.

Not the entire population of cells adapts to growing in suspension, but it is enough for some cells to adapt. The population of the cells that adapted to suspension will thrive and take over the culture little by little and that’s how we will reach our goal.

The downside to this process is that it can take a lot of time because it is a spontaneous process.

Orit:

And time is precious!

Idan:

Yes! From here we come to the second way to adapt the cells to grow in suspension and it is: Optimize culture conditions: During the adaptation process, the culture conditions, such as the type of media, the concentration of nutrients, and the presence of growth factors, are optimized to support cell growth and viability in suspension.

Orit:

Okay, so we need to give the cells the optimal environmental conditions that will help them to adapt to suspension. It’s like to growing babies actually. Ok so once you have adapted cells to suspension, how do you scaleup?  How can automation help rapid R&D to commercialization?

Idan:

Once we have found the optimal growth conditions for a particular cell line on a small scale, the large scale calculations come into play.

First we will perform a feasibility test: before scaling up, it is essential to conduct feasibility tests to determine if the process can be scaled up without compromising the quality of the product. It is important to evaluate the effect of the large scale on parameters such as oxygen transfer, mixing speed, uniform temperature distribution and other physical conditions. We will perform the feasibility test on a small scale.

Orit:

You mean little bioreactors?

Idan:

Yes, baby bioreactors.

After we have performed the feasibility test, the next step is to get the scale that is suitable for our process and will meet the final goal. We will achieve this by engineering calculations such as: shear forces, oxygen transfer coefficient, impeller size, vessel volume and more.

Regarding the second part of your question, automation and control is a very important aspect of bioreactor systems. In general, I see the bioreactor as a patient and I am the doctor, or in our case the veterinarian. Just as cows that are raised on the farm undergo periodic tests from time to time and have control systems in their bodies, everything is controlled in our process as well. The control and automation process includes sensors, controllers and software.

Orit:

So you have a lot of babies to take care of…

Idan:

Yes, many babies, but I’m a good father.

The sensors are used to measure process parameters such as: temperature, PH, dissolved oxygen and stirring rate. These sensors are connected to a controller that reads the data and adjusts to maintain the desired process parameters. If we go back to the concept of a cow, the sensors are the receptors in the body and the controller is the brain that sends the commands.

By connecting all the factors together we get a device that almost perfectly simulates the natural environment in which the cells grow in the animal’s body and thus we can grow cells from any animal whether it is a cow, a rooster, a pig or a fish. This is provided that we obtain the optimal environmental conditions for the cells and give them the feeling that they never left the animal’s body.

Orit:

Great! So your are the godfather of the cells. You talked about the scaling up the process but I know that for now it is really expensive. There are experts predicting that by as soon as 2030, cultured meat could have reached price parity with traditionally farmed meat. So now I can maybe take the lead and explain how to reach this goal and decrease the price.

Scaling up the production process of cultured meat has the potential to significantly reduce the cost of production. Currently, the cost of producing cultured meat is relatively high compared to traditional meat production methods. You probably ask why, this is mainly due to the high cost of the growth media and the equipment needed for production.

However, as the technology improves and the production processes become more efficient, the cost of production is expected to decrease. This could lead to a reduction in the price of cultured meat, making it more affordable for consumers.

One way to achieve this is through advancements in biotechnology, such as the development of more efficient growth media and bioreactors. Additionally, the use of plant-based growth media could reduce the cost of production, as plant-based materials are generally less expensive than animal-derived materials.

Moreover, economies of scale could also play a role in reducing the cost of production. As the production volume increases, the cost per unit could decrease due to bulk purchasing and other cost savings.

It is really important to note that price parity between cultured meat and traditionally farmed meat may not be the only factor that drives consumer adoption of cultured meat. Other factors such as taste, texture, and environmental impact may also play a significant role. Nonetheless, achieving price parity with traditional meat could be an important step in making cultured meat more accessible and mainstream.

Idan:

Orit, so from what I understand, the more you simplify the process and utilize more biotechnological factors, the cheaper the product will become.

Orit:

Yes, exactly.

Idan:

So we understood that the production cost need to be decreased. What are some of the ways that we can bring these costs down?

Orit:

The first way is to Develop animal-free growth factors: Growth factors are a key component in the cell culture media used for growing cultured meat. Currently, these growth factors are derived from animal sources, which can be expensive , limit scalability and it makes no sense to use them since we are generating cultivated meat to not hurt the animals, so research is being done to develop animal-free growth factors that can be produced more sustainably and of course at lower costs.

So the second way is to use plant-based protein sources: Some researchers are exploring the use of plant-based protein sources as an alternative to traditional animal-based protein sources in cell culture media. So plant-based proteins can be more cost-effective and sustainable, and may also improve the nutritional profile of cultured meat. That is also an important point and on our next Space we will talk about it.

Another way is to optimize cell culture processes: Advances in bioprocessing technologies and automation can help to optimize the cell culture processes used for producing cultured meat, reducing media costs and improving scalability. Such technologies already exist today.

To reduce the media cost we can also use alternative nutrient sources: Researchers are also exploring alternative nutrient sources, such as algae and insects, as potential sources of nutrients for cell culture media. These alternative sources could be more sustainable and cost-effective than traditional nutrient sources.

And finally Recycling the media can lead to a drastic media cost reduction: Currently, a significant amount of cell culture media is discarded after use. Recycling this media and reusing media can help reduce costs and improve sustainability.

So if we are looking at the big picture, these approaches represent promising avenues for reducing the media costs of cultured meat and making it more sustainable and cost-effective.

Idan:

Wow, Orit, it’s very interesting!

There are so many ways to decrease the cost and also play a major role in sustainability! 🙂

Is there a need for more collaboration and transparency between cultured meat companies and researchers?… which might potentially decrease the time necessary to reach industrial-scale production?

Orit:

Yes, there is a need for more collaboration and transparency between cultured meat companies and researchers to help speed up the development and industrial-scale production of cultured meat.

Currently, the field of cultured meat is still in its early stages, and there are many technical and scientific challenges that need to be addressed before cultured meat can be produced at scale. These challenges include optimizing cell culture processes, reducing production costs, improving the taste and texture of the meat, and addressing regulatory and consumer acceptance issues.

By the way, today the FDA gave a green light to another cultured meat company. So collaboration between cultured meat companies and researchers can help accelerate progress in these areas by allowing for the sharing of knowledge, expertise, and resources. For example, researchers can help companies develop more efficient cell culture processes or improve the nutritional content of the meat, while companies can provide researchers with funding, access to facilities, and real-world production challenges.

Transparency is also important in building trust and confidence in the industry, particularly among consumers and regulators. By openly sharing information about the production processes and ingredients used in cultured meat, companies can help alleviate concerns about safety, sustainability, and ethical issues.

There is a lot of collaboration and transparency between cultured meat companies and researchers can help accelerate the development of this promising technology and move it closer to industrial-scale production.

Let me see if we have any questions from the audience… not anymore. This was our last question for today, I hope you all enjoyed this space because I did and I’m sure Idan did also.

Idan:

Me too, it was excellent.

Orit:

I hope we were able to help you understand more about how cells can grow in suspension and what are the challenges we need to face to produce a large amount of meat. I look forward to the next biology space that will be about processes to generate fat and muscle cells, so I would like to special thanks to Idan! And I wish you all a great rest of your day. Hopefully we will meet you soon.

Idan:

Bye bye.