Organoid

Tiny organs as an alternative to animal testing

MDC researcher Dr. Stephan Preibisch and a team of scientists from Berlin, Bochum, and Düsseldorf have won the first round of the Federal Ministry of Education and Research’s “In Vitro Challenge.” The goal of the competition is to find clever alternatives to testing on laboratory animals. One bright idea is miniature organs created from human stem cells.

Organoids are miniaturized and simplified versions of organs. Just a few hundred micrometers in size and made up of no more than a few thousand cells, they are grown in the laboratory from human stem cells. Hopes are high that these mini-organs will revolutionize medical research and gradually obviate the need for animal experiments. The motives for driving this development forward are not only ethical; it also makes good medical sense. 

Human stem cells (ipS cells) can be transformed into neuronal precursor cells in the laboratory. If these cells can grow for 14 days in a hydrogel, they form "neurospheres", i.e. three-dimensional neuronal structures. The sphere then measures about 150µm in diameter. On the image taken with a lightsheet microscope, the cell nuclei can be seen in light blue. The microtubules, a component of the cytoskeleton, are stained orange. The cells come from the laboratory of neuroscientist Ellen Fritsche from the IUF - Leibniz Research Institute for Environmental Medicine.

Many findings derived from animal models cannot be directly mapped onto the human body. The German Federal Ministry for Education and Research (BMBF ) therefore recently called on scientists from a wide range of disciplines to put their heads together in a two-day workshop titled the “In Vitro Challenge” and come up with creative new approaches to the problem. The winning teams now have a year to put their ideas into practice with the help of up to €200,000 in funding. 

Team members didn’t know each other before the competition 

One of the prize-winning teams includes Stephan Preibisch, head of the MDC research group on Microscopy, Image Analysis & Modeling of Developing Organisms. Preibisch’s team, which includes four other researchers from Berlin, Bochum, and Düsseldorf, convinced the jury with its “EnVISIONaries” project idea. “The interesting thing about the competition was that the five of us had never met before and we all conduct research in completely different fields,” says Preibisch. “We conceived our project over just a single weekend. Now we need to flesh it out and find a way to make our idea work.”

The four other members of the team are its coordinator, Dr. Philipp Mergenthaler of the Charité’s Department of Neurology with Experimental Neurology; Dr. Annemarie Lang of the Charité’s Department of Rheumatology and Clinical Immunology; Professor Axel Mosig, head of the Bioinformatics lab at Ruhr-Universität Bochum; and Professor Ellen Fritsche, head of the research group on Modern Risk Assessment and Sphere Biology at the Leibniz Research Institute for Environmental Medicine in Düsseldorf. 

Artificial intelligence will keep the organoids alive 

We want our bioreactor to learn how to recognize when something has gone wrong with the system and to make the necessary adaptations independently.
Stephan Preibisch
Stephan Preibisch Head of "Microscopy, Image Analysis & Modeling of Developing Organisms" lab

The interdisciplinary team aims to use the ministry funding to develop a bioreactor within which artificial intelligence will keep the organoids alive and record their activity via high-resolution microscopy. “First, however, we need to find out what exactly the organoids require,” says Preibisch. “For example, what temperatures do these tiny organs need to thrive? How much oxygen do they need, and how much glucose? We want our bioreactor to learn how to recognize when something has gone wrong with the system and to make the necessary adaptations independently, without any input from us.” 

The researchers plan to work with two different kinds of organoids. On the one hand, they aim to use models of the human brain to gain a more thorough understanding of the causes and effects of stroke. They also plan to use cartilage models to learn precisely what happens in cartilage cells during the onset of arthritis and to postulate what biomaterials may be suitable for treating the crippling condition, or at least its symptoms. 

Both parts of the project require the cultivation of organoids over a sustained period of time as well as the automatic detection of relevant changes. “It would be of great benefit if this could be done using artificial intelligence,” says Preibisch. “That way, we wouldn’t need personnel taking care of the organoids around the clock.” 

Another application can be submitted to the ministry next year  

One of Preibisch’s contributions to the planned project will be to modify an invention developed by his research group at the MDC – a light-sheet microscope connected to a high-performance computer – in such a way that it can observe the organoids and record their activity for as long a period as possible. Another of his tasks will be to analyze the high-resolution 3D images obtained from the microscope. 

Preibisch and his colleagues now have until spring next year to make sufficient progress on their project to enable them to apply for multiyear funding from the ministry. They have much to do until then. “One important logistical matter that we have to find a solution for is the secure transportation of our in vitro models from one site to another,” says Preibisch. “Many of our planned experiments and analyses will take place in Düsseldorf, for example.” But it is precisely tricky questions like these that make EnVISIONaries such an exciting project for the MDC scientist.

Text: Anke Brodmerkel