Serum-Free Medium for Cultured Meat Production

December 15, 2020

Kai Steinmetz is a PhD candidate from the University of Auckland. In this episode, Alex Shirazi interviews Kai about creating serum free and cost-effective growth and differentiation media for cultured meat production, and establishing a deer primary muscle cell culture for the first time ever and test new media formulations on these cells. Transcript is below.


Also available on Spotify, Apple Podcasts, or wherever else you listen to podcasts!

Alex (00:04):

Thanks for joining us for the Cultured Meat and Future Food show. This episode is part of the New Harvest Fellowship series. We’re excited to have Kai Steinmetz on this episode. Kai is a PhD candidate from the University of Auckland. His research aims to create serum free and cost-effective growth and differentiation media for cultured meat production – both basal media and serum requirements will be addressed. His research will also establish a deer primary muscle cell culture for the first time ever and test new media formulations on these cells. We had a great chat with Kai on this next episode of the New Harvest Fellowship series. Let’s jump right in. Thanks for joining us on the Cultured Meat and Future Food show. I’m excited to have Kai Steinmetz on the episode today.

Kai (00:52):

Thanks for having me, Alex.

Alex (00:54):

Kai, Tell us a little bit about your background and actually when you first heard about cultured meat.

Kai (00:58):

Yes, my diploma was the German equivalent to a Master’s degree in biochemistry at the University of Frankfurt. I did basically just do structural bioresearch back then. It was just like looking at the structure of proteins on a molecular level. And when I was done with that, I was doing some soul searching because I didn’t really want to continue doing research in that area. And of course questioning the meaning of life and mine specifically, and where to take it next. Then during that time, I picked up my interest in philosophy again, which was something that always interested me like before I started doing biochemistry. In doing that, I came across the topic of animal rights and I saw the logic in that, and soon adopted that philosophy for myself and trying to cut out animal exploitation from your consumerism, you naturally start researching alternatives and you usually do that online. And that’s how I actually came across an article. I think the first thing that I actually found was Impossible Foods and them talking about how they were producing heme by microbial fermentation. Soon after researching down that line, I came across the topic of actually producing real meat in a lab. And that’s how I found New Harvest as well, and found out that some people were having much more ambitious ideas than I had initially thought. And yeah, having my new found ethical convictions and the right academic background to get into that, I was fairly sure pretty soon that I wanted to get involved myself.

Alex (02:31):

With kind of like the animal rights animal welfare in mind, sometimes we see that in different countries, the consumer perception is very different. How would you say that in New Zealand, people are open to vegan and vegetarian diets.

Kai (02:46):

So there’s certainly a difference between rural communities and cities when it comes to things like veganism and animal rights, because people in rural communities are usually having livestock here in New Zealand. This is very common. I think they get a bit defensive also when talking about this technology because well, naturally they feel threatened to some extent, but in the cities, there are actually very progressive communities that do support this research and what it really comes down to is trying to not give the individual farmers that might be threatened or feel threatened the idea that they’re going to be left behind, but instead show them the advantages of the technology and show them that there’s still a place for them and their land and their lifestyle in the future that we’re trying to build.

Alex (03:40):

Great. So once you heard about New Harvest, tell us a little bit about the program and what exactly you’re doing for your research.

Kai (03:47):

I actually didn’t get into the program right away. So what happened is that I followed the New Harvest newsletter, knowing that I wanted to get involved. I was watching that closely and at some point they advertised a PhD position in New Zealand and that was actually funded by a New Zealand research Institute. They just passed on the word because they wanted to have a bigger pool of candidates for that, obviously. And that’s how I met my current supervisor and applied for that position. And I got into the New Harvest Fellowship program after that to attract additional funding, to be able to visit more conferences and also to just be able to join the New Harvest network and be able to exchange ideas and problem solve together with all the other people in this community because the international community of fellows working in this field is still very small. So it’s really important to stay connected with those that are in the field and try and collaborate as best as possible.

Alex (04:52):

Cool, great. And when we had spoke last time, you were talking, I believe about different media options that you’re working with. Is that correct?

Kai (05:02):

Yeah. So when we are looking at serum free media, we can really split those into two groups. So they are chemically defined media and undefined media and in the chemically defined media, you know all the individual constituents and their concentrations and in the undefined, you don’t. You can further split these into animal product-free media, the undefined media, or just serum free, so you might have other animal products in there. Or protein-free, which is important if you want further downstream processing purify something like recombinant proteins. When it comes to trying to replace serum in the media and build a serum free medium, you really need to think about why you want to eliminate serum. And just to give you a few examples of what that might look like for stem cell therapies, people have been trying to get animal component tree media because they wanted xeno-free medium, which is something that doesn’t have any components in there from other species.

Kai (06:05):

So instead of using a fetal bovine serum, which is coming from cow fetuses, they have been using platelet lysates produced from human donor platelets. People usually donate these for patients, but they have a very short shelf life. Once they are no longer safe to use on patients, you can still lyse those platelets. And by disrupting these and purifying the liquid from them, you get something that’s very high in growth factors as well that you can use as an FBS replacement in stem cell therapies. When you look at chemically defined media, one example for these would be something like the production of high cost peptides in CHO cells, for example, and people really wanted to have a very reproducible process that is very optimizable because they have very high margins with the things that they’re producing. So even if a chemically defined medium might be more expensive liter to liter compared to an FBS containing media, the payoff is still worth it for them because they have much more optimizable system that are going to get more output with.

Kai (07:11):

And when we’re looking at meat production, we obviously want to get down the cost, but we also want to get rid of animal derived components for ethical reasons and defined and optimizable process would be nice, but it’s very hard to get something like that when you’re not even looking at a defined cell line or type. People have been using primary cell preparations from all sorts of species, you would expect them to have different, perfect solutions. So I think what people will be looking at is getting the most undefined media that they can get away with while going as defined as they need to. This ties in with what I said about trying to get farmers on board as well, because when I picked up my research, I actually thought that it would be beneficial to see if there is some application of agricultural byproducts that are produced in agriculture right now, as replacements for media components, so we can push down the cost by having something that’s not very well-defined, but still workable and allow this process to become more economically viable that way and going only as defined as we have to with other constituents, like grow factors. But obviously to know how defined you have to go, you actually need a defined medium as well. So I’m working on both of these things. So I’ve been testing byproducts from agriculture, for the application in these processes, as well as I’m looking at defined media.

Alex (08:44):

And for your research, are you looking at applications outside of cell cultured meat as well?

Kai (08:50):

No. I’m only focusing on cell cultured meat right now.

Alex (08:54):

I see. Okay. Over the long-term, is it true that even though these applications are for cell cultured meat, they could also be applicable to other industries or other types of research as well?

Kai (09:06):

Absolutely. It’s always the case that when you’re having research in one area that you have cross pollination, so to say with other research areas, so there’s a lot of lap over with especially tissue engineering that’s happening. So whenever we’re looking at, how can we make muscle grow in a lab, which is basically what meat is, this is something that is of interest to people who want to grow muscle for other applications rather than eating it of course.

Alex (09:35):

Absolutely. And so when we hear about startups that are going into pilot scale production, that seems to be quite a bit of a theme for 2020, what type of solutions do you think that these startups have resorted to when it comes to their growth factors? Have they cracked the code for media at this pilot scale level?

Kai (09:55):

Yeah, I think when you hearing about plans for pilot scale production, you’ve got to be a bit cautious because you can always plan things without knowing all the minutiae. So I can plan a trip and I don’t necessarily know what type of car I’m going to rent for that. And I can also cancel my plans. I realized down the line that I don’t have the money for the car, that the car alone would just get me from London to Singapore, but I’m of no doubt that people have found workable solutions for the type of cells that they’re working with. But as I said before, I’m not really sure there’s going to be the code for cell culture media. I’m more of the opinion that there’s going to be various different solutions for the different cell types people are looking in. And also these will need to adapt to the mode of production as well. So when you’re trying to grow something on a lab scale, it might have very different media compositions than what you might be looking at for stirred-tank production in a bio-reactor for example.

Alex (10:55):

I do love that analogy. I wish some, maybe some investors would think about that as well, because you might be planning a trip where you might rent a car when really all you can get around with is a bicycle. Well, we’ll see what happens. I want to ask you about the different phases of your research. How long is your program and what are kind of like the milestones you’re planning to reach, if you could even look at it that way,

Kai (11:23):

The program is for three years funded and I have another additional a year that I might be taking for completion if I’m not finished in time, but obviously COVID has changed plans because when you’re not allowed to get out the house, it’s really hard to do lab work. You can always write things, but yeah, it’s very hard to make progress. At some point when lockdowns persist, I might be looking at getting an extension for that as well. So obviously the first milestone I would like to accomplish soon as having my literature review published. So people have something that summarizes the current research on a serum free media for muscle stem cell production. And yeah, next big milestone that I’m actually wanting to do is finalize and also at some point obviously publish a defined medium for muscle cells, the type of cells that I’m working with. So I’m looking forward to that.

Alex (12:20):

Cool. And are there any other graduates that are, I guess, PhD candidates or researchers that are in your program also working on cell cultured meat

Kai (12:31):

In, at the University of Auckland right now? Yeah. We have one Master’s student who has been working alongside me, Vicky Andriessen. She’s been looking at LAM cells and also at scaffolding. We wanted to have another PhD start here, but with the very harsh travel restrictions that New Zealand has right now, it’s been really difficult for her to get started, but there’s recently been a program that allowed 250 PhD and Master’s students to enter New Zealand and we’re hoping she gets into that.

Alex (13:02):

Cool. Yeah. And Vicky is awesome. So that’s very cool that you’re working with her.

Kai (13:06):

She is.

Alex (13:06):

In addition to New Harvest, what are some of the other programs or resources that have helped you get started in this kind of cell cultured, not only industry, but phase of research

Kai (13:17):

New Harvest has really been awesome. And just like I said, being able to go on the Slack channel and have access to all these people who are working on very related issues is just great. And what else helped really was probably Twitter because people retweet something new and exciting when they find something new. So getting a feel for who the players are in that space and what they’re trying to do, that’s really helpful. And last but not least of course conferences. So New Harvest 2019 was pretty great. And the Cultured Meat conference was awesome as well. And I would encourage everyone who wants to who’s just in this and does know how to get started, wants to get started, to try and get into one of these conferences and see what’s what, especially with how the Cultured Meat conference was online and very reasonably priced. There’s really nothing that prohibits anyone from going there and making connections with people and trying to figure out where they might fit in this space.

Alex (14:17):

Oh, you mean the Cultured Meat symposium?

Kai (14:19):

Oh yeah, yeah.

Alex (14:19):

Oh yeah. And were you able to chat with a lot of people while you were there?

Kai (14:23):

So I got to chat with a few people, but I had some issues with time zones, so hard to join talks when they start at 5:00 AM. That’s not usually when I’m up.

Alex (14:32):

Right. And right now you’re on Friday, I’m on a Thursday. So it makes it even more complicated.

Kai (14:38):

Yeah. Other than that, not something I’ve used extensively myself, but the Good Food Institute has a section called essential reading and research. So anyone who wants to learn more should probably check that out as well.

Alex (14:51):

Cool. And I think our podcast might be listed in that essential reading and research

Kai (14:56):

It should be, if it’s not, that’s an oversight.

Alex (14:59):

Yeah. I think it is. I think it is. Great. You know, you mentioned Twitter and it’s really interesting to see how valuable Twitter is for science and all types of science. And I feel like Twitter is a way the science community really shares information really fast. And I haven’t really seen that in too many other industries, I guess if you don’t include politics.

Kai (15:19):

Yeah, definitely. So Twitters really good for really the retweeting is probably the best feature of it because you can just amplify and show something that you found interesting. Yeah. Without having to jump through too many hoops. So it’s really something to go down the rabbit hole as far as you want.

Alex (15:40):

So how does scientific progression typically take place? And what I mean by that is that, will there be certain breakthroughs that just might speed up the process within the industry overnight, so to speak? Or is it always a slow and steady path forward?

Alex (15:56):

I don’t think it is ever a steady path because when you zoom out far enough, just the scientific and the technological advancement in other areas, it’s going to be exponential. So we are at the very start of that process so it’s hard to see just yet. And if you zoom in, though, I think this imaginary line of progress is surely to be checked. There will be some pivotal findings and techniques born out of scientific discovery, things like PCR, polymerase chain reaction, or CRISPR. These have really been huge jumps in scientific research and it’s not unreasonable to expect something like this happening in this space as well, but that won’t necessarily be born out of the research, just focusing on this topic as well. Like I said before, there’s huge overlap with the field of tissue engineering and even breakthroughs in more loosely related fields like renewable energy might be absolute game-changers for cellular agriculture. So if you’re looking at suddenly having the greatest, most clean and abundant power source of all time, that’s really gonna accelerate these processes.

Alex (17:07):

Cool. And that’s very motivating, not just optimistic but realistic, but really exciting thing to think about that we could have these breakthroughs, like you mentioned, PCR or CRISPR that could help us really do a lot more.

Kai (17:21):

Yes. I’m really looking forward to that.

Alex (17:22):

So now actually it’s time for our audience questions. And so if you have submitted a question, we will try to answer it. We have two questions on this episode and for future episodes, especially on the New Harvest fellowship series, we’ll be having a call out for questions. So feel free to take a look at the upcoming episodes, but we have a question from Lisa from Australia. Go ahead, Lisa.

Lisa (17:47):

Hi Kai, this is Lisa from Australia. I have a question about growth factors. Have you already been able to induce proliferation and differentiation in your DSLs? And if so, are you able to talk a bit more about the key media components or growth factors needed for each process? Thanks.

Kai (18:03):

Yeah. Good question. So I’ve been able to isolate and induce proliferation and differentiation in the muscle stem cells. And I also saw spontaneous contractions of differentiate muscle tissue the other day, which was really exciting. So yeah, it’s working. Yeah. When it comes to the media needs, I can’t say I’ve completely cracked the code yet, but they don’t seem to behave significantly different from other primary muscle stem cells e.g. from cows, which kind of makes sense because they’re very closely related. So for my bio nerds out there, they’re from the same infraorder, the Pecora, I don’t anticipate huge differences. So I haven’t made them proliferate and differentiate in a completely defined system yet. But what I can say up until now is that definitely have rate positively in terms of proliferation to the basic fibroblast growth factor, which is something we see in almost all muscle stem cells across species.

Alex (18:58):

Great. And our next question is from Kieren also from Australia. Go ahead, Kieren.

Kieren (19:03):

Hey, it’s Kieren from Australia. How complex a growth factor proteins. Currently, at least some are manufactured in mammalian cells, Chinese hamster ovary. But could they be produced with the correct post-translational modifications in yeast or algae. That way perhaps used to algae, which are hydrolyzed for the provision of biomass for media, could also cheaply provide the growth factors as well. Thanks.

Kai (19:27):

Great question. I must admit though that I haven’t gone into depth about the structure of growth factors and the molecular machinery necessary to produce them myself because that’s beyond the scope of my current research. A lot of the growth factors that I’ve been looking at are already produced in e-coli though, and I’m sure that people are already working on strain engineering of microorganisms and other ways to get around using mammalian cells for that production, because like you said, it’s the most expensive way to get to that. Shout out to, ORF Genetics from Iceland, who’ve recently been on this very podcast as well. Listen to the episode if you haven’t. So one of the ways to produce these growth factors in bulk might actually also be in barley, who knows. It’s a very exciting technology and I’m very keen to see that progress. I also think that we might not necessarily stick to the growth factors as we find them in nature in the long run.

Kai (20:21):

So when getting more discoveries in terms of small molecules, who might fit these receptors for the growth factors as well, this might lead to much more stable or even more potent reactions in our cells. And of course, cheaper ways to drive these desired signaling pathways, the solution of the future might not necessarily be the same complex growth factors that we’re looking at right now. Who you might be wanting to talk to about this is Cameron Semper. He’s also a New Harvest Fellow and he’s actually looking at producing fish growth factors in e-coli for serum free production of fish meat. So maybe someone to have on the podcast next.

Alex (21:05):

Great. I love it. Nice shout outs too. So thank you, Lisa. And thank you Kieren for submitting the questions. My next question for you, Kai, and this is a question that I’ve asked a couple of the other New Harvest Fellows and other guests on this show. Pre-COVID, if we were to walk into your lab or go to your bench, what would we see?

Kai (21:27):

Probably a lot of bottles, different things, and also a lot of paper because I keep printing protocols and then I don’t put them away nice and neat so they’re usually quite disheveled, but I try and keep the chaos to my bench in the lab that’s not the sterile hood and yeah, most of my work has actually been happening in the sterile hood. So you always got to be very neat about that. Wipe it down and UV it, so there’s nothing in there that might grow in your cell culture media, although you didn’t want it to grow. Yeah. That’s definitely a bit of a schizophrenic thing happening between my lab bench and the clean bench.

Alex (22:08):

You could learn more about Kai on LinkedIn and about New Harvest at Kai, do you have any last insights for our listeners today?

Kai (22:19):

Yeah. So I’d like to actually speak to your listeners and say that they’re probably like the top 1% of people informed about this subject. If they’re listening to your podcast and as such, I think it would be really cool if they could spread the word and try and be an advocate for this technology as well because people see articles out there and they might’ve heard of cultured meat, but they don’t really know a lot about what’s going on. And I think not only for getting more public funding and more public awareness for the scientific process, it’s also really important that this research is demystified. People need to eventually accept these products that are coming out of this process. They need to be informed. The earlier this happens the better and that’s on the early adopters to facilitate.

Alex (23:12):

Kai. Thank you so much for taking the time and sharing your insight on the Future Food show.

Kai (23:17):

Thank you very much for having me.

Alex (23:19):

This is your host, Alex, and we look forward to seeing you on our next episode.


Transcribed by New Harvest volunteer Bianca Le. 

To stay up to date on New Harvest research updates and events, sign up for our newsletter.