hDMT INFRA
hDMT INFRA
Human cell-based models are a potential game-changer for many healthcare applications. Academically, the Netherlands is at the international forefront of this highly multidisciplinary field. The national hDMT consortium represents and unites scientists from its 16 partner organizations; these (technical) universities and UMCs each have unique expertise and facilities, which together can offer stakeholders, from model developers, biotech to end-users (e.g. pharma), an unprecedented toolbox to implement complex human cell-based models in their R&D. hDMT INFRA facilitates and structures knowledge utilization and application by establishing a national framework of Service Centers of Expertise (SCEs) in all hDMT-partner organizations, with complementary expertise.
Infrastructure and User Services
We establish a durable infrastructure that will provide support for innovation development and end-user application of dynamic human models. The individual SCEs will be independent, with their own portfolio, but embedded in the national infrastructure framework. Services depend on each SCE’s specific expertise, e.g. tailored advice andaccess to manufacturing facilities, training and education, and, in the future, independent testing and qualification. The initial INFRA SCEs include the hiPSC & OoC hotel in Leiden, the ErasmusMC iPS Core Facility in Rotterdam, UPORT, Utrecht Living Technologies (all part of hDMT INFRA StemCells), and the OoC Center Twente (part of hDMT INFRA OpenTech). Together, they offer support and access to customized hiPSC generation including gene-editing; access to living biobanks of adult stem cells and organoids; expert support with the implementation of AI for life sciences applications; and services for Organ-on-Chip design, prototyping and testing.
These SCEs serve as a blueprint for the addition of new SCEs with complementary expertise, tools, data and knowledge. Finally, to make the unique datasets generated publicly available – required by the European Medicine Agency (EMA) for the use of dynamic human models in regulatory approval processes– hDMT INFRA is working towards setting up and maintaining a FAIR-based database. Ultimately, the aim of hDMT INFRA is to offer a complete collection of tools, data and knowledge that will be available to all users to support development of new, validated and qualified dynamic human models for any organ and disease for research and pre-clinical development purposes.
Examples/description of the type of research
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, microphysiological systems (MPS), now widely postulated as providing beyond state-of-the-art model systems for healthcare research. The first drugs developed, based entirely on human cell models without experimental animals, have already received market approval.
Dynamic human 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 and progression in humans as well as form the basis for accurate diagnostics. These models are thus expected to continue to contribute to reducing the need, cost, and ethical burden associated with animal studies. Showcases, like the human Heart MPS model for cardiotoxicity tests, are now emerging that clearly demonstrate the superiority and complementarity of MPS to current model systems. Furthermore, hDMT INFRA also brings together experts in ethical and legal aspects of developing human cell-based organ/disease models, aiming to create a national framework for consent, material sharing and collaboration.
How to access the infrastructure?
Users can access hDMT INFRA via the Central Hub or via a searchable catalogue of SCEs on the hDMT INFRA website. Access to the infrastructure will incur fee-for-service to cover costs and ensure sustainability, with differentiated pricing for academic (cost-recovery) versus commercial (market conform) users of the infrastructure. Fees will be used to ensure the long-term sustainability of the infrastructure and ensure ongoing accessibility and availability for all users. hDMT INFRA is open to explore possibilities for financial support from the Dutch government (ZonMw and NWO) to stimulate open access of the SCEs for Dutch researchers.