cientists from the Hubrecht Institute, the University of Utrecht and Mimetas have successfully grown kidney tubules derived from human kidney adult stem cells in microfluidic chips. Henriette Lanz, director of biology

at Mimetas and co-author of the paper explains: “Scientists at the Hubrecht Institute managed to reprogramme stem cells found

in the human kidney cortex to cells that are similar to tubular cells of the kidney. From these cells, my team has grown three- dimensional perfused kidney tubules. We have discovered that these tubules are fully polarised, meaning that they distinguish inside from outside, just like in a real kidney. Moreover, the biologically important barrier function of the kidney tubes is intact. We show that transporter activity is functional, which is a hallmark of kidney tissue, responsible for pumping of nutrients and toxicants across the kidney barrier. We can grow 40 of such tubules in one single OrganoPlate. The kidney tubes can be used to create disease models that allow the development of novel therapies. This novel technology offers


mall infections can be fatal: millions of people die each year from sepsis, an overreaction of the immune system. A new immune signalling molecule, designed by a research team from the Technical University of Munich (TUM), now provides the basis for potential new approaches in sepsis therapy. Researchers around the world have long been searching for new therapies. An interdisciplinary team from the fields of structural biology, immunology and cell biology has now, for the first time, successfully produced a protein that could balance the overshooting immune response. In their work, the scientists were inspired

by evolution: mice are well protected from sepsis by their immune systems. Here, interleukins – messengers that mediate communication between the cells of the immune system – play a key role. “The interleukins are the vocabulary with which immune cells communicate,” explains Matthias Feige, professor of Cellular Protein Biochemistry at the TUM. The cells form these messenger molecules according to a very specific blueprint of individual amino

acids. Their arrangement determines which three- dimensional structure an interleukin adopts and, consequently, which information it transmits. Humans and mice

have similar, yet different vocabularies. The researchers discovered one striking difference in interleukin-27-alpha. This molecule can be released by cells of the mouse immune system but not by human cells and regulates immune cell function. “Using computer models and cell

biological experiments, we discovered that a single structurally important amino acid defines whether interleukin-27-alpha is released by cells of the immune system,” explains Stephanie Müller, the first author of the study. “That gave us an idea about how we can engineer novel human interleukin proteins that are released by cells so that we can produce them biotechnologically.”

a powerful human alternative to animal testing for toxic side effects of new medicines.” A mini kidney from the lab doesn’t look

like a normal kidney, but the simple cell structures share many of the characteristics of real kidneys. Researchers can use them to study certain kidney diseases. “We can use these mini kidneys to model various disorders: hereditary kidney diseases, infections and cancer. This allows us to study in detail what exactly is going wrong,” says Hans Clevers, professor of Molecular Genetics at Utrecht University and the University Medical Center Utrecht, and group leader at the Hubrecht Institute. “This helps us to understand the workings of healthy kidneys better, and hopefully, in the future, we will be able to develop treatments for kidney disorders.”

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The team then prepared the modified interleukin in the lab and tested its biological functions – with very encouraging results: the engineered messenger molecule is recognised by human cells. First analyses suggest that it can indeed balance an overreaction of the immune system, making it a promising candidate for sepsis therapy.

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