Good morning, pioneers!

Here’s what we’ve got for you in this month’s email:

• FAT! And why it’s good (for studying disease)

• Unresolved challenges with 3D adipose tissue

• The WORC Community is live!

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Let’s get into it 🧬!

KEY OPINION LEADERS

3D Models of the Most Communicative Organ in the Body: Fat  

This month, we sat down with Dr. Elvira Weber, adipose tissue organoid pioneer, expert in regenerative medicine, and Head of Lab at the CURE 3D lab in Düsseldorf.  

Birth of the 1st Adipoid 

Who are you and how did you get into the field of 3D culture? 

Dr. Weber: My name is Elvira Weber. I’m a biologist. I did my PhD in biochemistry and then moved on to a postdoc in virology. At that time, I started working a lot with animals. I switched to the lipid field in 2014. I wanted to study the interaction between macrophages and adipocytes. I started working with adipocytes in 2D cell culture, but I realised that they didn’t look anything close to what they would look like in-vivo. 

So, I decided to start a side project to find another method for culturing adipocytes without going back to animal experiments. Around the same time, I heard a talk from Hans Clevers for the first time. He was working with organoids, which sounded interesting. 

I started checking to see if it was possible with adipose tissue. I found all sorts of organoids, but not for adipose tissue. That's still a problem today, because a lot of people don't realise that adipose tissue is a full organ. They normally think of it as something that is between your other organs, but few realise its important function. 

It's the most communicative organ. It sends out adipokines through our body, communicating with every organ.

When you check which kind of pathologies you find with adipose tissue connected, it's not just cancer or cardiovascular diseases. It's also Alzheimer's, Parkinson’s, and even blindness. It's involved everywhere. 

So, I decided to try making adipose tissue organoids myself. I was a bit naive. I thought it was something you just do. It turned out to be more difficult.  

It was several years ago, so we were really in the beginning of the organoid movement. First, I needed to decide whether to use a scaffold or not. I realised that I wanted to do lipid metabolism, which is better without a scaffold. Then I thought about using hanging drops, magnetic beads, or whatever else - I tried them all.  

None of them worked. 

It took me about four years to find the solutions. And I can just say thank you very much to my old boss, Professor Christoph Thiele. I came every week saying I was going to try something new and super fancy. And the week after I would come and say that it didn't work out so well... for years. It was crazy. 

That was the starting point for how I came to CURE 3D. The head of the clinic for Cardiac Surgery, Professor Lichtenberg, had this innovative idea that a clinician, in this case Prof. Hug Aubin - a heart surgeon - and a basic researcher – me - lead the lab together. It’s a wonderful concept since we learn a lot from each other, and it helps our research improve a lot. 

What is your main focus now? 

Dr. Weber: Our lab has several working groups. One is working with bioprinting. The plan is to print small tissues, like vessels and valves. We are focused on different bio inks and cross-linking. 

Another group is working on decellularised aortic valves. Professor Lichtenberg was already involved in developing the method to remove intact valves from a patient with heart failure, decellularise it, and implant it into another human. Because there are no cells, there won't be an immune rejection. 

And that is working seriously well. It's an amazing project because you don't need any anticoagulants anymore. It also grows with the patient, which is important for transplantation into children. We’re still improving the process by testing different coatings and understanding the immune reaction in the patient. 

We also have a biobank. Patients who come to our clinic sign a consent form that allows us to collect tissue samples and store them in the biobank. This is important because we can use patient material to better understand what organs and tissues consist of and how they function. 

And then there is one working group that works with organoids. Our focus here is on adipoids, the importance of adipose tissue for cardiac function, and to understand the differences between different adipose tissue fat depots. 

Key challenges with adipose tissue organoids 

What are the key challenges when it comes to scaling up your work? 

Dr. Weber: You always have to be careful with standards. Your models have to be the same so you can compare them and standardise your testing. How they’re handled is also important. We're thinking of using robotics, but it's difficult for us because adipoids are the only organoids that swim. Once you have a nice adipose tissue, it will swim up. It's a good quality control for us because we know they really have fat inside. But it makes it hard when you're trying to use robotic pipettes. So, it’s something you need to do manually at the moment. 

I'm still waiting for somebody to develop a cool robot that can find my adipoids, avoid sucking them up, and still do a medium change. It would be lovely to have a tool like this. 

What are some of the missing pieces when it comes to tissue regeneration that have yet to be solved? 

Dr. Weber: We're in the beginning right now. I’m super optimistic, but there’s a lot to do. First of all, your starting material. You can’t do this with cell lines. A lot of people go for iPSCs. I'm not a huge fan of them myself, since it’s difficult to go back to human with them because of their possible tumorigenicity. They also don’t fully mature.  

Standardisation and immunogenicity as well. One thing will always be time. You need to think of how long it will take you to regenerate new tissue from a patient's sample. Typically, you have an acute injury, and you can’t wait. So that will always be a problem. 

Vascularisation hasn’t been solved, so you can’t go big. And the regulatory side when you want to go back into human. 

What do you see people get wrong when they try to commercialize new products in the field of tissue regeneration, or 3D culture more broadly? 

Dr. Weber: I have less experience here than you would probably think, because my outputs have never been patented. Now, I see that a lot of companies are trying to do it. At the time, I thought I should, but like many young researchers, I didn’t know how. 

I've seen good and bad things from the people who do it. It always depends on the company and the researcher. How well they work together. I think it’s far more important that researchers from industry and from academia connect with each other. And that it’s not all for selling, but also for developing tools. 

Don’t get me wrong, I'm always happy about industry being at conferences, because I learn a lot there about new products and I love talking to my colleagues. It would just be great to engage more on the development side. To see how we can help one another. 

Because people don't have to make the same mistakes. We might try something that doesn’t work, so we don’t publish it. But we can share that information, so others don’t do the same. This is missing at the moment.  

Dr. Weber’s Top 3D Culture Events and Resources 

Outside of your own lab, who are the people, groups, or organizations that you look to for inspiration?  

Dr. Weber: I was a huge Twitter fan before it changed because there was a great science community there. LinkedIn also works well. Most of my inspiration comes from conferences. In Germany we have a good one from EMBL called Organoids. There is also a huge international one, the IMPSS. 

My most favourite one is organoidspheroid.com. It's a website. They started in the field early and I love what they're doing. They're collecting all papers together, so you just click on your organ of interest and then you can see the newest relevant papers.

They have a conference once a year called World Organoid Research Day+ (WORD+). It's amazing! It's a great group of scientists who all want to share and collaborate with great ideas. 

Final thoughts?

Dr. Weber No, but I really like what you’re doing here because newsletters from companies will get more interest from people like that. 

Read Dr. Weber’s full interview here. 

COMMUNITY

World Organoid Research Community (WORC)

The WORC Community was launched by the founders of organoidspheroid.com. It’s quickly becoming the global network for organoid and organ-on-a-chip researchers.

The community is packed with useful resources, protocols, papers, and webinars.

You can sign up for the WORC community here and connect with researchers worldwide.

RESEARCH

Exciting research that has advanced 3D cell culture recently:

Cool research in the field of 3D cell culture that you think would benefit the community? Reply to this email to discuss featuring it in our next issue.

EVENTS

Don’t miss out on these upcoming events in the 3D cell culture space:

That’s it for this month!

We’ll be off in August, so see you again in September.

Wishing you all a great summer ☀️

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