What’s the focus of your current research specifically?
It’s two-fold, but very much intertwined. On the skin side, we work on things like melanoma, skin allergies, eczema, burns and healing wounds. On the dental side, we assess the safety of materials used in dentistry. Take dental implants, for instance: we can use our research to predict adverse reactions and make better implants.
And for both of these we use animal-alternative methods, specialising in immunity models and organ-on-a-chip technologies. Every day, we’re challenging the technology to represent the human situation better and better, in all its complexity. Skin is one of the leaders in the field of tissue engineering, but we can also use it to help the development of other organoids, like gut models, lymph nodes and brain organoids, for example. And we want to expand into the field of multi-organ technology.
Which types of patients can benefit from your research?
I’ll give you a couple of examples. If you lose a tooth, the dentist will implant a screw into the bone and place a false tooth on top. This all needs to attach to the gum, otherwise it will get infected and fall out. Our models allow us to test the quality of the implant and false tooth when it comes to attaching to the soft tissue. Another dental example: if you have a dental wire, some nickel could leak out and cause an allergic reaction. We culture oral mucosa in order to test these things.
Outside of the dental industry there are plenty of other applications. For instance, we’ve been working with the Dutch Burns Foundation for many years, and we’ve cultured skin grafts to treat burns patients. Right now, we’re running a big project to test saliva in in vitro skin models to treat burns wounds in a way that leads to less scarring and infections. It makes sense when you think about it: if you cut or burn your finger, the first thing you do is lick it!
Which other organisations are you working with?
In the past, we worked a lot with patients directly. But now, we’re working more with industry: we create the models for companies to test their products on. A big pharmaceutical company might have developed a new peptide to heal wounds, or a cell-based therapy for cancer – and we can help the company test the treatments using our models. Or we can help them identify new drug targets by testing molecules mechanistically with our models. Essentially, we discuss with medical device companies and pharmaceutical companies what they want to study, and then develop models to reflect the disease profile they want to test.
How close are we to replacing animal trials with these models?
In the cosmetics industry, that transition has already happened. Animal testing for cosmetics in the EU was all but banned in 2013. Before then, products were tested on mice and rabbits, and scientists had to figure out how to safely test products on humans. Now, there’s a valid in vitro system for testing irritants and allergens without using animals – which just goes to show what’s possible.
In the medical industry, this has not yet happened because they don’t want to inhibit new drug development. But the drive and momentum is there, so I see things moving forward quite quickly. And with our human models, the data correlates far better to a human patient than it does with an animal model. After all, mice are not the same as humans – we have different skin, our tumours behave differently, our immune system is different and so on.
But some fields are moving faster than others. Skin got a head-start because of the cosmetics industry, and it’s relatively easier to create skin models compared with brain models, for instance. For skin and mucosa, replacing animal trials will happen sooner rather than later, but it’s more complex when you want to work with other organs as well. When it comes to vaccines and immunology, these are challenging areas that have different timelines. But it will happen: everything is possible when you have the mindset and the finance.
Are there ways for scientists and society to come together on this?
Yes – one great example is a recent “Helpathon”, which is like a hackathon but for health sciences. I work with Transition Programme animal-free Innovations (TPI), and many people from TPI’s network came together to work on animal-free models. A Helpathon consists of a two-day workshop covering two different research questions from scientists who are employing animal research, and we work together to find alternative techniques that reach the same goals without using animals. The Helpathon brings together not only scientists but also financiers, sustainability entrepreneurs, the Dutch Burns Foundation, Proefdiervrij (the Dutch Society for the Replacement of Animal Testing – DSRAT), students – really anyone who’s interested. And at the end of it you have a network of collaborators for that scientist to work with in the future to make the transition to animal-free techniques.
The Helpathon has been such a success that it even won the international Lush Prize in 2020, with the jury selecting the TPI Helpathon team for inspiring and helping so many researchers to rethink their research in terms of animal-free methods. We’ve organised four Helpathons so far, and are planning a fifth in 2022 – so do get involved!
What’s your biggest challenge right now?
We’ve just had a large number of projects granted – mostly relating to organ-on-a-chip technology – so we’ll be focusing on those in 2022. Our biggest challenge will be to bring in the immune system. And for that we need vasculature. To give an example: in tumour metastasis, we can mimic the invasion of the tumour from the dermis to the epidermis but not yet to the lymph nodes.
Essentially, the challenge is to traffic the immune cells from the blood vessels to the tissue, and from the tissue into the lymph nodes. Every disease is immune-related, so you need vasculature along with circulating immune cells in order to make a good organoid model.
Where can people go to find more information?
I’d urge you to take a look at the websites of three of the main research consortia we work with:
- The Institute for human Organ and Disease Model Technologies (hDMT) is a pre-competitive non-profit technological R&D institute in the Netherlands, which integrates state-of-the-art human stem cell technologies with top-level engineering, physics, chemistry, biology, clinical and pharmaceutical expertise from academia and industry to develop human organ and disease models-on-a-chip.
- The LymphChip Consortium is formed by hDMT researchers, and it’s envisaged that the organ-on-a-chip models with integrated lymphatics can be applied as a precision tool in the battle against immune-related diseases.
- Transition Programme animal-free Innovations (TPI) is made up of 10 partners aiming to make the Netherlands world leader in animal-free innovations. TPI focuses on the transition from animal testing to the use of technologies such as organs-on-a-chip or artificial intelligence (and combinations of the two).
- A Helpathon is an action-oriented rapid prototyping method derived from hackathons. Together, the TPI Helpathon team, Mister Lion (an Amsterdam-based lab for societal change) and parties interested in biomedical innovation have organised a series of successful Helpathons to help researchers make the shift towards animal-free innovation.
Interview by Vicky Hampton, December 2021