Steakholder Meets: from one cell to scale

Orit

Hello everyone and thank you for joining us, we will start shortly. Let’s wait a few seconds to let people join in and the speakers as well. Yoni and Maya, 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, and I will be hosting Steakholder Meets. In today’s episode, I am excited to have our Molecular and cellular Engineering Team leader, Dr. Yoni Moskovitz, and his team member, Maya Finkel.

After our last Space, we talked about the cell, the source, the isolation, the growth, the characterization, and our challenges; today we’ll discuss the following process that takes us from isolated cell to a cell line. 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.

Maya, Yoni – welcome! I am excited to have you both here today. First, let’s start with a quick introduction.

Can each of you tell me a few words about yourselves, how you got into food tech in general, and Steakholder foods specifically? Yoni would you like to start?

Yoni:

Yes, thank you. I am Yoni Moskovitz, and I am the team leader of Molecular and cellular Engineering. I hold a PhD degree in life science from the Hebrew University since 2010 with a background in molecular biology and stem cell biology and after many years of academic research, I decided to join Steakholder because it combines cutting edge technologies both from the bio-printing & molecular aspects.

Maya:

Hi, I’m Maya Finkel, an R&D scientist in the Molecular and cellular Engineering team. I hold a master’s degree from the Faculty of Agriculture in Biochemistry and Food science. I’m very passionate about the Food Tech industry and about sustainability in particular. I decided to join Steakholder Foods to implement my knowledge in molecular biology to make the world a better place.  

Orit:

As I mentioned, in our last space, we talked about the cell – how we source it, isolate the stem cells, and choose the ones that are the best fit to become fat and muscle cells. Today, we will continue this journey and understand how isolated cells become a CELL LINE. My first question is precisely about this – what is a cell line?

Yoni:

First, I would like to remind you that to generate cultivated meat we need to mimic the native tissue composed of fat and muscle cells. As previously mentioned, we are using different types of stem cells to generate fat and muscle cells and combine them together to generate as a final product whether it is a steak, hamburger or any other type of meat. When we talk about a commercial product, we want to make sure we are buying, in our case eating, biologically identical product all the time. Cell line is defined as a uniform and stable cell population, holding uniformity at the cell morphology, that ca can grow indefinitely and have a short population doubling time.e last character implies that the cells are in their optimal physiology. It is defined as the time needed for the cell population to double itself. This parameter is called population doubling time, The shorter & the stable it is, the better. Cells isolated directly from the tissue are called primary cells. Those cells can be either multipotent cells that have a short lifespan or pluripotent stem cells with a longer lifespan. The multipotent cells know how to fulfill their pre-dedicated destination as 1 or 2 different cell types like heart, kidney, muscles, or adipocytes cells and in some point, they know that their time has come and they stop dividing.

In order to make those cells proliferative indefinitely, immortalization is needed. In the opposite, pluripotent stem cells, like embryonic stem cells, can proliferate indefinitely and keep their differentiative potential at any time. Indeed, this type of cell can differentiate to all the cells existing within the body. These cells are then being expanded to millions of cells creating our cell-line bank, so it can be thawed upon demeaned, and can serve as a reliable and stable cell source for mass production.

To create a steak, meatball or any other type of meat product, billion of billions of fully differentiated cells to muscle and fat are needed. So, if we want to create a stable and unchanging source of cells, we need to have immortalized cell lines.

Orit:

Thank you, Yoni, so now we understand what a cell line is, cells that can proliferate meaning duplicate indefinitely and why we need those cells to create cultivated meat.

Can you explain the process of taking an isolated cell and turning it into a stable cell line for cultivated meat production? Yoni, do you want to take this?

Yoni:

Creating an immortal cell-line from a single cell, can be originted from different cell sources. One of the cell origins is  embryonic stem cells. These cells have the unique ability to proliferate indefinitely and to keep their stemness status, which means that they can differentiate to any other cell as required.

A second possible cell origin can be iPSCs, induced pluripotent stem cells, these cells can be derived from fully differentiated cells and with amazing technology can go back in time and to have the same properties as the embryonic stem cells.

The third option reaching the golden throne is by spontaneous immortalization this way goes through an extensive and prolonged passages of cell culture over time. At some point, some cells will get spontaneous mutation at realtered cell cycle regulation genes and will acquire an evolutionary selective advantage over the other cells in the population.

Orit:

Okay, so you can either isolate or establish an immortalized cell line in the lab by different ways. But what is the challenge to make it a cell line?

Yoni:

One of the challenges is that our cell will keep their characteristic from the beginning until the end. I mean the cells should have a low doubling time and should keep their abilities to differentiate into fat and muscle even after a lot of passages.  Another challenge is that our cell-line originated from adherent cells, which means they naturally need the support of other cell types around them creating a niche. However, the need for a robust & cost-effective meat production obligates that the cell will be able to grow, in suspension with media that fits the cells.   After a long adaptation process and by using unique media, Steakholder scientists succeeded in getting several cell-lines that can well proliferate also in suspension. Another important challenge is the need for media cost reduction. Formulating a cheap, serum free and without animal derived growth factor is one of our main concerns in the food industry. We believe that combining cells suspension with serum free media will lead to a mass production of thousands of edible and sustainable bovine biomasses.

Orit:

Okay, so you make these meat cells in your lab, how can you ensure the cells remain safe to eat?Maya do you want to take this question?

Maya:

First, we perform various tests to ensure that lab grown meat is safe to eat. We are controlling every step of cell production; we are working in aseptic conditions and trying to use only edible reagents. During the whole process, we conduct extensive tests like testing different pathogens such as viruses, bacteria and other pathogens that can cause foodborne illness. In addition, toxicity tests are performed to ensure that it does not contain harmful chemicals or toxins for humans. Moreover, we make sure that Lab grown meat will have the same nutritional values as conventional grown meat. We perform different tests to ensure that it meets the established standards. A product cannot arrive on the market without the approval of food regulatory authorities such as SFA/FDA/EFSA. Before arriving at the market, a dossier containing all the informations regarding the cells, the process and the safety of the product, is submitted to those authorities. The regulatory authorities are highly qualified to check all the information and to decide if the data provided in the dossier is robust, consistent and give enough proof to testify regarding the safety of the product.  Upon dossier consent, the green light for commercialization is approved.

Orit:

Great, so I think we understand that all the food we eat is fully controlled by the food authorities and it is safe.  We have a question from one of our listeners: What is the cost of producing cell lines for cultivated meat?

Maya:

The cost of producing cell lines for cultivated meat is still high compared to traditional animal farming methods. All the food meat industry is struggling to reduce the cost. The main reason to the high price is due to the media in which the cells are cultivated. This media contains a lot of reagents that were produced in the beginning for cell therapy in order to transplant the cells to humans and not for the food industry.   A lot of companies all over the world are working hard to provide animal free reagents with cost effectiveness. In the future, the cost of producing meat in a lab will also decrease as the upscale process improves gradually as well as the animal free materials will be developed. The scale up process of cultured meat requires further research & development to improve the cost effectiveness of the products. I believe that in the future, the cost of culture meat will decrease and become the same as traditional farming. More importantly, the cultured meat industry is a more moral and healthier way of living.

The most significant benefit of a lab grown meat is the reduction of the environmental impact. The cultured meat industry reduces the time and resources used to raise cows in traditional methods. In the cultivated meat industry, land would not be needed, and less water would be consumed.

For example nowdays, the production of 300 grams of entrecote or sirloin through traditional farming requires the cultivation, watering, and feeding of an entire herd of cows, and this results in significant financial and ecological impacts. The meat industry is considered as the no.1 cause of global warming due to the methane gas that the cows produce. And also, the financial cost, which is enormous.

In contrast, for 300 grams entrecote or sirloin, we will need 300gr of biomass, grew under controlled & monitored environment at our bioreactors. This biomass can be expanded from only one frozen vial. So, the environmental impact is minor, and the financial cost will be highly reduced.

Orit:

Thank you, Yoni, and thank you Maya.

I hope this topic is clear and since there are no other questions from the audience, we will wrap it up. We will continue this scientific series about cultivated meat, but our next Space will be in two weeks, on Tuesday, March 7th about women in science and business. So stay tuned on our social media platforms.

Thank you all for listening. Aurevoir