Science and industry are constantly striving to end the use of animal testing in toxicological research. As part of these efforts, researchers at Wageningen have worked with Unilever to develop tiny, three-dimensional organs for laboratory use. They even contain a blood-like fluid rich in nutrients. These mini-organs are expected to replace some animal tests and make it possible to investigate the effects of chemicals, medicines and nutrients on the human body.
From a scientific perspective, human bodily processes are different to those of test animals, which means the results of animal tests don’t always reflect how the human body will respond to a particular substance. And from a social and ethical point of view it’s also preferable to minimise the use of animals for this type of research. Some products, such as cosmetics, are already subject to regulations that ban the use of animal testing.
Mini-organs in 3D
In the past, risk assessments for chemicals or other substances were based almost entirely on data derived from animal tests, but in recent years there's been a shift towards using data derived from experiments on human cells in test tubes or petri dishes. Scientists use these methods to study how those cells react to chemicals. But those models have their limits. They are based on just one cell type, while real organs always consist of a multitude of cell types. Cells in petri dishes are also arranged in a single, flat layer rather than as a three-dimensional structure.
That’s why Wageningen University & Research (WUR) and Unilever are working together in the lab to produce tiny 3D organs featuring multiple cell types and fluid flows. “The mini-organs are also referred to as organs-on-a-chip, and they are clusters of cells at a micrometre scale,” explains Hans Bouwmeester from WUR’s Toxicology department. “Tiny channels provide the cells with a flow of liquid containing oxygen and nutrients, just like in the human body. These tiny channels, also known as microfluidic systems, are now being rapidly developed for a range of purposes. But at present they're not being used much by scientists for toxicological risk assessments of chemicals or other substances. Our aim is to make that possible by optimising these mini-organs.”
The process as a whole is more complicated than simply designing the technology, because regulations need to be considered too. In many cases, animal testing is required in order to prove that products and substances are safe. “We want to show that our mini-organs, combined with computer modelling, can provide an adequate simulation of human tissue functions and biological reactions to chemicals,” says Bouwmeester.
Wageningen University & Research is conducting the research in collaboration with Unilever’s Safety and Environmental Assurance Centre (SEAC). “The challenge is to generate a robust scientific evidence base for these mini-organs, leading to widespread acceptance of them,” says Paul Carmichael at SEAC. “That means assurances for European authorities that they can make reliable decisions based on these new methodological risk assessments.” Eventually Unilever wants to be able to test all of its products, ranging from personal care products to new plant-based food products, without animal testing.
Ecosystem for experiments
“Wageningen University & Research is a logical partner for us because it has unique expertise at the interface of technology and biology,” says Carmichael. On the purely technical side, both parties are involved with hDMT, the Dutch organ-on-chip community which also includes other partners such as the universities of Delft, Twente, Utrecht and Leiden.
“Through our partnership with Wageningen we want to continue building an ecosystem for trying out new concepts and approaches,” explains Carmichael. “Not just through this new project, but also through the work being done by PhD candidates already working at Wageningen.”
Bouwmeester adds: “It’s much bigger than just this new project. This partnership has come at a time when other new projects are also being launched by the Dutch Research Agenda (NWA). Through this project we’re discovering what businesses need, which then enhances our research. Conversely, we’re developing technologies that they can actually put into practice. Industry professionals and regulatory authorities are equally eager to see what these new mini-organs can do.”