The topic of Organ-on-chip fits into the strategic research agendas of several Top sectors such as AgroFood, High Tech Systems and Materials (HTSM) and Life Sciences and Health (LSH) and is therefore well embedded in TNO research in several roadmaps and research programs. TNO has an Early Research Program (ERP) Organ-function-on-a-chip, which is a vehicle in which TNO renews and maintains its knowledge base, with an emphasis on intensive collaboration with knowledge partners and stakeholders. In addition to the ERP, organ-function on a chip technologies are embedded in the following roadmaps:
• Within the Roadmap Predictive Health Technologies, predictive complex human models, such as organ-on-a-chip, are relevant for two business lines : Faster into humans, and Personalised therapeutic interventions.
• Within the Roadmap “Food and Nutrition”, organ-on-a-chip technology will be relevant especially for activities within the business line Food and Health, and in later stage for Food Safety, Urbanisation and Human Enhancement.
• several TNO Roadmaps develop technologies that will find applications in Organ-function on a chip models.
• Within the Shared Research program “van ‘t Hoff”, various optical imaging methods for medical applications are currently being developed (such as ring resonators and AFM).
Evita van de Steeg
Added value for hDMT
• expertise in (systems)biology
• understanding of the effect of interventions on disease pathways
• the knowledge and expertise on how to translate in vivo animal to human data. This can help in faster translation of in vitro data towards human data and result in better predictive models. Currently, the focus of TNO is on liver (NASH), gut (incl. microbiome) and lung (also with host-microbiome interactions), these areas are complementary to the current focus of hDMT.
• extensive network in the Pharma and Biotech Industry
• help with matchmaking between academia and industry
• knowledge and expertise on implementation of alternatives for animal testing
• linking with regulatory bodies and the Dutch Top Sectors.
Added value of hDMT for TNO
• easy access to available state-of-the-art technologies, knowledge and expertise of different (academic) partners
Expertise and facilities
TNO is internationally recognized partner for system biology, disease pathways and models, innovative read-out technologies and a personalized health approach. Within TNO specific expertise and technologies that are relevant for the development of organ-on-a-chip platforms are present. TNO harbors high level knowledge and technologies regarding biological systems, organ function, and disease development. The technologies include advanced in vitro (human cells, tissues, microbiome), in vivo (humanized animal models, human studies) and in silico (systems biology, PBPK modeling, etc.) systems, as well as various unique analytical tools (3D printing, -omics, accelerator mass spectrometry, imaging) which are highly relevant for generation, validation and application of organ-on-a- 2/3 chip technology. Furthermore, TNO harbors technologies such as microfluidics and optical imaging which will be highly relevant for the automation of screening tools and development of online readout systems. Also the 3D (bio)printing expertise at TNO is very useful to develop more sophisticated chips by printing specific scaffolds or even printing cells in 3D to form a more physiological organ model.
Relevant (inter)national collaborations, in public and private sector
• Liver: a consortium between TNO, Takara Bio Europe AB (Cellartis) from Sweden and InvitroCue Pte Ltd, from Singapore. Takara focusses on the development of technologies and know-how related to selection, maintenance and differentiation of hiPSC (including culturing systems and conditions), the genome engineering of hiPSC and the differentiation of hiPSC into specific cell types such as, cardiomyocytes and hepatocytes. InvitroCue provides innovative products and services in the fields of in vitro DMPK, in vitro toxicology and digital pathology utilizing cell-based models and image analysis tools.
• Lung: In addition, there is a consortium of TNO Triskelion BV, University of Utrecht, LUMC, Epithelix, Nickel producing industrial companies and TNO in a translational project on the Mode of Action of Nickel.
Gut: consortium consisting of Dutch academia (Hogeschool Utrecht, Utrecht University, and WUR) and several technology providers (TNO) and food industry, working on the development of better in vitro intestinal models to assess health effects of food ingredients.
• I. M. Kooter, M. Grollers-Mulderij, M. Steenhof, E. Duistermaat, F. A.A. van Acker, Y.C.M. Staal, P. C. Tromp, E. Schoen, C. F. Kuper and E. van Someren: Cellular Effects in an In Vitro Human 3D Cellular Airway Model and A549/BEAS-2B In Vitro Cell Cultures Following Air Exposure to Cerium Oxide Particles at an Air–Liquid Interface, 2016, DOI: 10.1089/aivt.2015.0030
• J. Westerhout, E. van de Steeg, D. Grossouw, E. E. Zeijdner, C.A. Krul, M. Verwei, H. M. Wortelboer: A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices. Eur J Pharm Sci. 2014 Oct 15;63:167-77. doi: 10.1016/j.ejps.2014.07.003.
• M. Reitsma, J. Westerhout, H. J. Wichers, H. M. Wortelboer, K. C. Verhoeckx. Protein transport across the small intestine in food allergy. Mol Nutr Food Res. 2014 Jan;58(1):194-205. doi: 10.1002/mnfr.201300204
• G. Grootaers, R. Ostendorf, I. Bobeldijk, R. Hanemaaijer, I. Kooter, H. van de Sandt, E. van de Steeg, C. Krul. The 3 dimensions of organ on-a-chip. TNO White paper 2016
• RAAK-PRO grant for collaboration regarding the development of better in vitro intestinal models to assess health effects of food ingredients.
• TNO ERP Organ-function on a chip
• Stichting Proefdiervrij and ZonMw (VIMP) grant for valorizing the 3D human primary bronchial epithelial cell (PBEC) model developed at the LUMC