Mimicking the structure and physiology of human tissues and organs in the laboratory. Microphysiological systems (MPSs), such as organs-on-chip (OoCs), offer this unique opportunity but determining the relevance of MPS to actual tissues of the human body has remained challenging. Experts from reNEW Leiden and other Dutch academic centers affiliated with Netherlands Organ-on-Chip Initiative (NOCI) now advocate adopting standards that make comparisons between models possible in the scientific journal Nature Biomedical Engineering .
MPSs can emulate the physiology and structure of organs and tissues of the human body. They offer possibilities to measure physiological features of tissues and organs and test how these are affected by disease or new drugs. Nevertheless, most studies using MPSs so far have been descriptive. “We believe it is time to take the next step and develop measurable standards that allow us to compare different MPSs directly and assess their relevance to the human body. Only then can MPSs become an accepted model to test drugs or gain new knowledge about disease in humans,” says Professor Christine Mummery, reNEW Leiden PI and senior author of the study.
Designed and emergent features
In the article, the authors distinguish two types of MPS features which they term “designed” and “emergent”. Researchers can directly influence designed features, such as oxygen levels, fluid flow or organ dimensions, by changing the design of the model. If technically feasible, the features should be as close as possible to values measured in the human body. By contrast, emergent features describe cell functions that cannot be fully controlled by the operator, such as electrophysiological properties or barrier functions of cells. These features develop autonomously but can be monitored with specialized sensors and readouts.
Vessel, Gut, Brain and Heart
In the article, the researchers use vessel-on-chip, gut-on-chip, brain-on-chip and heart-on-chip as examples to illustrate designed and emergent features in MPS models. For these systems, where each tissue originates from one of the three germ layers, they discuss specific features that can be quantified. Mummery: “We highlight quantifiable features where the measurement method or values are very similar in MPSs and the human body. These can be used to form standards that have accepted predictive value for human physiology to, in the future, identify and test potential new drugs.” Importantly, the article also highlights technological advances that could further improve, or enable the accurate design and quantification, of these physiological features.
Future outlook
Researchers are increasingly using MPSs in biomedical research. It is therefore becoming progressively important to carefully select and record choices in the design of MPSs. Mummery concludes, “With this publication, we emphasize the importance of implementing measurable standards in MPSs. We provide guidance in selecting the right model for each scientific question: specifically, is the model “fit-for-purpose”. By doing so, we hope to contribute to the implementation of these systems for drug development in the future.”
