Fraunhofer magazine 3.19 - 49 It seems like an act of creation. For Dr. Christopher Probst, however, it’s all part of the job. Probst has just taken a dish with cell cultures from the incubator. He slides the cultures carefully under the microscope and observes how the thin tissue of transparent cells pulsates. The stem cells have differentiated to cardiac muscle cells. “By the time the cells are two weeks old,” Probst explains, “you can see, with the naked eye, the whole slide beating like a pulse!” Probst is a research fellow at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB in Stuttgart. He is part of the Attract working group, which is led by Prof. Peter Loskill. If successful, the group’s research may well substantially reduce the number of animal experiments. (see interview, right). Doctoral student Oliver Schneider will use the cardiac muscle cells to create a so-called organ-on-a-chip (OOC): postage- stamp-sized polymer chambers in which minuscule tissue cultures and organoids are fed with nutrients via a system of microchannels. Back in 2016, OOC was declared one of the top emerging technologies by the World Economic Forum. Today, there are OOC systems for a whole range of tissue types, including cardiac muscle, liver, kidney and even brain tissue. The working group at Fraunhofer IGB has helped spearhead this technology in Europe, pioneering a number of unique developments that include the recreation of human fatty tissue and human retinal tissue on a chip. Loskill is pursuing an ambitious goal. He first began working on OOC technology in the USA back in 2013, where a huge funding program had just been launched. This saw a number of research organizations team up with federal and public bodies for a variety of projects. The Food and Drug Administration (FDA), for example, saw OOC as a means of speeding up drug development, whereas the U.S. Department of Defense was interested in tests for chemical and biological weapons. The Environmental Protection Agency (EPA), meanwhile, wanted ways of investigating pollutants. Buoyed by hundreds of millions of dollars in funding, U.S. researchers soon forged ahead of the rest of the world, including Europe. Loskill is now seeking to redress the balance. Together with three fellow researchers from the Netherlands, he set up the European Organ-on-Chip Society in November 2018. This was followed by an inaugural conference in Stuttgart. Furthermore, EU funding has now been secured for two undertakings: a Marie Curie project involving 21 European partners, and an initiative to draw up a road map for OOC technology in Europe. This collaboration between European research groups will help pave the way for a broad-based application of this technology. And now that scientists have mastered the “Substantially fewer animal experiments” Prof. Loskill, will organ-on-a-chip technology help reduce large-scale animal experimen- tation? For sure. We’re already seeing a big interest on the part of the pharmaceutical industry. The tech- nology can be used right across the board: screening for new active ingredients, carrying out toxicity tests and backing up clinical studies. Will the regulatory authorities accept organ-on-a-chip data in place of results from animal experiments? The regulatory authorities are very open to this new technology. I’m currently working with regulatory bodies on two EU projects. These include the German Federal Institute for Drugs and Medical Devices (BfArM). Will the technology make animal exper- iments completely redundant in the long term? No technology alone will ever be able to com- pletely replace animal experimentation. But our chips do provide a source of data that will enable us to gain requisite certainty with significantly fewer animal experiments. “Many diseases manifest themselves in different ways in male and female patients,” Prof. Peter Loskill explains. His research may well lead to the development of gender-specific therapies. © Bernd Müller / Fraunhofer IGB technique of placing a whole variety of tissue cultures on a chip, the next challenge will be to increase the throughput of the various substances being tested. Doctoral student Schneider is already working on ways of scaling up this technology. In the future, so-called organ-on-a-disc systems will combine hundreds of human tissue samples in one handy format, thereby helping to turn this technology into a routine procedure. Teaching a chip how to see The latest breakthrough to emerge from Loskill’s lab is a retina-on-a-chip system, featuring the complex stratified tissue of the human retina as an organoid. Right now, Loskill and his team – which includes doctoral student Johanna Chuchuy – is busy endowing it with the capacity to see. Working with partners from the University of Tübingen, they have been able to differentiate stem cells and incorporate them in a chip in such a way that they recreate a multilayer tissue. This tissue comprises, among other things, light-sensi- tive rods and cones, retinal pigment epithelium and ganglion cells, which make up the optic nerve. “When we shine light on the retina-on-a-chip, we register an electrophysiological signal in the rods and cones,” Loskill explains. “And now we’re working on a system with which we can quantitatively measure this signal.” Such a system will make it possible to measure the extent to which a substance influences the “visual capacity” of the ret- ina-on-a-chip. “The pharmaceutical industry is showing a big interest in retina-on-a-chip technology,” Loskill adds. “Lots of modern drugs have retinopathic side effects.” To date, model systems are rare in this field. Animal models, for example, are of only limited use since the retina of animals has a different structure than that of the human retina. Moreover, retina-on- a-chip technology will also facilitate research into diseases of the retina and the development of drugs to treat conditions such as age-related macular degeneration and diabetic retinopathy.