Creating systemic in vitro models is a major challenge for medical research and drug development. While human cell cultures offer accurate representation on a cellular level, they lack the complexity and connectivity of a real organ. Animal models, on the other side of the spectrum, are inherently systematic, but are poor stand-ins for human biology. Michelle Jäschke, PhD student at TissUse GmbH in Berlin, is trying to bridge this gap in the laboratory by creating multi-organ-chip devices that combine human cells with the systemic complexity of actual organs.
The technology that Michelle uses in her research comes from TissUse, a Berlin-based biotech company founded in 2010 that specializes in developing different types of multi-organ-chip devices for use in research.
― The multi-organ technology enables us to cultivate several organ models within one microphysiological system. Each chip contains multiple compartments that are interconnected through microfluidic channels, and each of these compartments can contain different cell types. So, it is possible to cultivate liver cells in one compartment, intestinal cells in the next one and kidney in the third one, and all of them are connected, says Michelle. ― Our approach is human and systemic, meaning that we use human cells for the organ models and combine this with a systemic multi-organ-chip.
Michelle came to TissUse for her master’s thesis work, after having studied biochemistry for her bachelor’s and master’s degree, the latter which she received from Freie Universität Berlin. It was here that she came into contact with kidney research, developing iSPC-derived renal models. This work continued into her current PhD project, which focuses on developing a perfused, multi-organ-chip-based renal model – a kidney-on-a-chip – as part of the BIRDIE project.
― My role in the project is the development of a novel multi-organ-chip that enables the cocultivation of a perfused, 3D-printed tubular interstitium with a liver model under physiological conditions, with the core focus on designing the actual chip, says Michelle.
When describing the project, Michelle explains that she has been able to use her previous experience working with iPSC-derived renal models in a way that has enabled her to take a large responsibility in the project already at an early stage. ― I have been working with kidney models since my master thesis, so when I started the project, I already had a clear vision in my mind of what kind of chip I would like to develop during the project to really take advantage of the integration of a 3D printed model, which enables us to pursue different approaches than we usually do.
Michelle says that what she has really enjoyed about the project is how it brings many different and fascinating methods together. ― Each of the methods that we employ, such as the multi-organ-chips, the iPSCs, the 3D bioprinting and the spatial transcriptomics, is already really exciting on its own But I think it is the combination of all of them that makes this project special.
One of the ways the BIRDIE project combines different technologies is by incorporating iPSCs into the multi-organ-chips, something that creates exciting opportunities for personalized medicine applications, Michelle explains. ― IPSCs can be generated from any patient and can be used in a patient-specific chip, which can then be employed to investigate which therapy is best suited for that specific patient, says Michelle.
― Another major advantage is that using iPSCs enables us to incorporate an immune system component into our multi-organ-chips, Michelle continues and explains that when you work with cell lines, the cells all come from different donors, which means that inclusion of immune system components will lead to rejection, something that can be avoided if all the cells are derived from the same donor.
An important goal for Michelle when it comes to designing novel in vitro technologies, is being able to provide a better alternative to the use of animals for research purposes. There is a great interest within both the research community and the pharmaceutical industry to find alternatives to animal testing in research and drug development. There are many reasons behind this growing interest, such as more accurate data, reduced costs and animal welfare.
― Most people in this field care about animal welfare. I don’t think you end up working in this field by chance. To me, animal welfare has always been important and definitely acts as a personal motivation, Michelle says.
What Michelle hopes to see, at the end of the BIRDIE project, is a tubulo-interstitium model validated for disease and nephrotoxicity studies that can be used across many different research areas. ― I believe that is an ambitious, yet realistic, goal.