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Spotlight on Research: A synthetic, animal-free way to grow 3D organoids
Researchers from the Hubrecht Institute and Radboud University have developed a completely animal-free gel to grow organoids, miniature 3D versions of organs.
What is the question you are trying to answer?
Obtaining human tissue to study organ development and disease can be challenging. Organoids are small, 3D tissue structures grown from stem cells in the laboratory, which provide researchers with alternatives and opportunities for this kind of research. They require carefully controlled growth conditions, such as special nutrients and structures to grow on.
Researchers created a new material for growing organoids by incorporating part of a bacterial protein called invasin into a gel. Invasin works by activating pathways in the cells that help them establish polarity: spatial differences in shape, structure and function. For example, in the intestine, the cells have two sides, the ‘apical’ and ‘basal’ sides, which must face in the right direction to form a functional intestine.
The researchers showed that the new gel performed just as well as traditional materials for growing intestinal and airway organoids.
Joost Wijnakker
PhD Student
Hans Clevers
Oncode Institute
Hubrecht Institute-KNAW & University Medical Center Utrecht
Why are you investigating this question?
Until now, most organoid research has relied on Matrigel or BME, gels made from mouse tumours. Although they are effective, these materials are expensive, can vary between batches, and depend on animal sources - millions of mice per year. Some other studies have tried to find alternatives, but they often lack data to show that their materials work over a long period of time, to start cultures from tissue biopsies or for different organoid types, which are important requirements for growing organoids.
In 2024, researchers in the Clevers group showed that invasin could be used to grow organoids in 2D on flat surfaces. This approach is ideal for large-scale screening and drug testing. Now, researchers have worked together to show that this invasin molecule can be incorporated into an animal-free PIC gel developed by the Kouwer group, allowing organoids to grow in 3D, just like they do in animal-derived gels like Matrigel and BME. Growing organoids in three dimensions means that they better represent the complex structures of real human organs, making them a more effective research model.
What will the next steps be?
Many properties and applications of this new gel still remain to be explored. The initial study focused on human intestinal and airway organoids; the next steps will involve optimising it to better support other organoid types, building on the work that has already been done.
What impact do you hope for this to have in your field?
There are many applications where this gel could be used:
- Some research in regenerative medicine has explored the potential for organoids to be grown in the lab and transplanted into humans, but this cannot be done using organoids grown using animal products. The new gel may open doors for this kind of research.
- Organoids could be used in personalised medicine - for example, cancer organoids could be grown from patient tissue biopsies and used to determine the most effective treatment for each individual in the lab.
- A cheaper and more reliable gel means that organoid drug screening could be made more affordable and effective.
By replacing animal-derived materials with a synthetic alternative, this breakthrough makes organoid research more consistent, ethical, and affordable. It opens up exciting possibilities for drug testing, tissue transplantation, and fundamental studies of human biology, all without relying on animal products.
Learn More: Animal-free perspectives for organoid culture - PhD Defense Joost Wijnakker