Researching diabetes and pancreatic cancer with miniature organs

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NewIn: Matthias Hebrok

NewIn: Prof. Matthias Hebrok.
NewIn: Prof. Matthias Hebrok.
In this issue of "NewIn," we introduce Matthias Hebrok. The professor of Applied Stem Cell and Organoid Systems and director of the new TUM Center for Organoid Systems (COS) creates organ-like structures from stem cells. He uses these organoids to research pancreatic cancer, develop diagnostic methods and work toward insulin-producing cells for stem cell therapies.

Measuring around 120 micrometers across, the cell clusters that Matthias Hebrok produces from stem cells in the laboratory are barely discernable by the naked eye. The artificially formed three-dimensional structures are quite like those of the pancreas in our bodies - "to nearly 90 percent," says Hebrok. In our bodies, these so-called islets of Langerhans perform vital chores: Among other things, they produce insulin, the hormone that signals our cells to absorb blood sugar. "In diabetes, the insulin-producing beta cells of these structures are damaged. That’s why we are working on rebuilding and improving beta cells so that they can be used for cell replacement therapies in the future."

A personal motivation for diabetes research

Matthias Hebrok developed the urge to get to the bottom of things at an early age. "My father was an inventor and tinkerer. He was always thinking, how can something be made better? How can this or that problem be solved in a particularly clever manner? He was a master craftsman and worked with machines - now, I’m thinking, how can that work in biology?" says Hebrok. "Unfortunately, my father suffered from diabetes for many years. For me, that is also a personal motivation to work on the disease - to keep this from happening to others."

Hebrok kicked off his research career in developmental biology. As a postdoctoral fellow at Harvard, he began to investigate diseases of the pancreas in increasing detail. For more than 20 years, Hebrok researched and lectured as a professor of diabetes research at the University of California San Francisco, where he directed the Diabetes Center from 2010 to 2020. On September 1, 2022, he was appointed Professor of Applied Stem Cell and Organoid Systems at TUM and heads the newly founded Center for Organoid Systems (COS). He is also the director of the Institute for Diabetes and Organoid Technology (IDOT) at Helmholtz Munich.

Organoids: Miniature organs from the laboratory

Under suitable laboratory conditions, stem cells can be used to produce something akin to miniature versions of our organs: so-called organoids with self-organized, three-dimensional cell structures. "At first sight, a stem cell looks completely unspectacular. But under the right conditions, within a few weeks it will develop a cell structure analogous to those we have in our bodies: for example, a part of the pancreas. I still find it absolutely intriguing how you can reproduce something living in this way to cure diseases. In the U.S., first clinical trials are underway for stem cell therapies with artificially generated beta cells. It is wonderful to be working on something that contributes to this goal."

Replicating tissue and determining how tissue becomes morbid are the two main areas Hebrok and his team are focusing on. For example, they are also investigating how cancer develops in the pancreas and how to ward it off. "Pancreatic cancer is particularly insidious because it is often detected very late. Using organoids, we can closely study this disease and how it develops outside the body. In this way, we hope to facilitate earlier diagnoses and develop therapies that we can test directly within human organoid systems."

Staying curious, being courageous and keeping an eye on the big picture - Hebrok’s enthusiasm for research is palpable, even after more than 30 years of research. "That feeling when you see something that no one has ever seen before and develop something that can really help in a medical sense. That is really amazing and gratifying."