To achieve our aim and make optimal use of current expertise and facilities in the Dutch OoC ecosystem we will establish a durable OoC infrastructure that will provide support for innovation development and end-user application. The individual CoEs will be self-sustainable, but embedded in the national infrastructure framework. They need dedicated equipment and staff, who offer expert services in OoC design and application. These services are dependent on the expertise of the specific CoE and include tailored advice and access to manufacturing facilities, training and education, and, in the future, independent testing and qualification. The initial business case is now being developed for two recently initiated CoEs, the OoC Center Twente (OoCCT) and the iPSC & OoC Hotel in the Leiden University Medical Center (LUMC), that will serve as blueprints for future CoEs. These centers have complementary expertise and will facilitate researchers and companies in application of OoC technology. The other hDMT partners have also developed complementary technology, and will follow as CoEs in a stepwise process. Depending on the expertise of the CoE, different types of equipment, biobanked cell collections or data will be made available. The OoCCT has a strong focus on standardization and making OoC technology available, and on providing services and tools for chip design and manufacturing. The iPSC & OoC Hotel by contrast, has a strong focus on generation and repair of (diseased) human (stem) cell lines and their derivatives, cell culture within OoC systems, training of end users and independent qualification of OoC models. To make this nationally available, systems and organization for iPSC banking, automated cell culture robotics, dedicated staff but also training facilities are required. Finally, to make the qualification data publicly available – required by the European Medicine Agency (EMA) for the use of OoC in regulatory approval processes– setting up and maintaining a database is needed. CoEs that will join later will offer different services and innovative technologies but together they will serve as a complete collection of the tools, data and knowledge available to all users to support development of a wide range of new OoC models for any organ and disease, qualify such models for regulatory purposes and/or identify existing models that have been qualified based on published data.
Regarding the research, we refer to question 101 of the Dutch National Research Agenda for the route Regenerative Medicine: Can we design models of the human body and use smart technology for health-, nutrition- and toxicity research, and at the same time drastically reduce the use of animal experiments? The answer is: Yes, that is possible. Emerging at the junction of sophisticated technologies, including tissue engineering with human adult- and induced pluripotent (iPSC) stem cells, advanced cell sensors, microfluidics and microfabrication, OoC technology is now widely postulated as providing beyond state-of-the-art model systems for healthcare research. OoC models can recapitulate aspects of human physiology and pathology accurately for use in drug discovery, efficacy and toxicology testing and precision (or ultimately, personalized) medicine with view to improving existing bioassays and providing new insights into underlying mechanisms of disease development and progression in humans. In addition, OoCs may contribute to reducing the need, cost, and ethical burden associated with animal studies. Showcases, like the human Heart-on-Chip model for cardiotoxicity tests, are now emerging that clearly demonstrate the superiority and complementarity of OoCs to current model systems. The recent publication Mini Organs-on-Chips, initiated and coordinated by hDMT in collaboration with the Dutch Foundation for Biosciences and Society, gives an impression of the state-of-the-art of OoC technology in the Netherlands, and its perspectives for the future.