VU University Medical Center
The VU University Medical Centre (VUmc) is one of the leading academic centers in the Netherlands and focuses its core activities on healthcare, research and education. VUmc increasingly adopts a multidisciplinary approach to care: consultation, diagnosis, and treatment plan can be completed in a single visit to the clinic or outpatient department. VUmc research is strongly translational: from bench to bedside to society. VUmc's studies focus on discovering, testing, implementing and disseminating new insights and on improving health care.
The joint mission of VUmc
The interdisciplinary research institutes of VUmc (VUmc Cancer Centre Amsterdam, Institute for Cardiovascular Research and Amsterdam Movement Science) join forces within hDMT to develop models for basal and translational research, identification of novel drug targets and testing safety and efficacy of novel compounds. Clearly for this to be a success, physiologically relevant human disease models are required. Even with the exceptional embedment of organ-on-chip technology within the VUmc research policy, we realize that we cannot achieve our goals alone and our scientists and students will greatly benefit from collaborations offered within hDMT
Added value for hDMT and vice versa
In particular, VUmc has expertise in culture of human healthy and diseased organotypic models, (tumor) immunology and angiogenesis. These are care areas of expertise which hDMT is aiming to include within the national institute. VUmc is looking forward to collaborations with the public and private sector via hDMTs network, in particular with TUs and SMEs, which will lead to innovative project ideas and valorization for all involved. In addition to moving science forward, hDMT will provide VUmc PhD students and young PostDocs with an excellent opportunity to be involved in multi-disciplinary science activities and networks enabling them to orientate better their future career pathway.
Expertise and facilities of the applicant relevant for Organ-on-chip
Expertise Immune competent skin-on-chip
immune competent human full thickness skin equivalents are employed in fundamental skin biology, toxicology, allergy, fibrosis and risk assessment studies. Our state-of-the-art model containing Langerhans Cells, is currently being incorporated into devices made in collaboration with Micronit BV and Phillips Research. Use of the Fluigent S.A. pump system will enable continuous circulation of immune cells e.g., monocytes and Iymphocytes, in the microfluidics compartment Iined with endothelial cells. Once the model has been established and shown to be stable for at least 2 weeks, it will be further developed into skin disease modeIs (melanoma, fibrosis, tumor angiogenesis) and combined with still to be developed oral mucosa, gut and Iymph node-on-chip.
This model (and variants thereof) is being developed and implemented in the department of Physiology in collaboration with Prof Lopez, (Seattle), LifeTec Group and Micronit B.V. The model consists of PDMS (polydimethylsiloxane) stamps and collagen which allows vessel network formation including branches and bifurcations. The model will use endothelial colony-forming cells isolated from peripheral blood to allow analysis of patient-specific endothelium. The model also allows co-culture with smooth muscIe cells and pericytes which we will be used for studies on intercellular crosstalk in the context of aging and vascular pathology. These 3D vascular models are being developed towards future drug and personal care product testing platforms.
VUmc has excellent facilities within the new 0/2 building on the VU campus which is named after our symbol of life, oxygen. In the 0|2 Building researchers from VUmc, VU University Amsterdam and the University of Amsterdam jointly tackle socially relevant issues in the field of Human Health & Life Sciences. In this state-of-the-art shared research environment, 0|2 provides a rich mix of fundamental and applied scientific-medical research conducted by cell biologists, immunologists, chemists, molecular biologists, analysts, physiologists, anatomists, biophysicists and bioinformaticians from the two universities and preclinical departments from VUmc. The second research cluster in VUmc is located in the Cancer Center Amsterdam research building. Tumor-host interactions, the microenvironment and mechanisms of immune suppression are major research themes. The multidisciplinary character of the VUmc-CancerCenterAmsterdam (CCA) ensures both the required oncological and immunological expertise and tools. Due to the close vicinity of the two research centres within VUmc, a dynamic hub has been created for translational research with excellent collaboration between clinicians and fundamental scientists from 26 disciplines which also ensures access to samples of human healthy- (rest material from OK) and diseased tissues and organs.
Currently, organ-on-chip activities are concentrated in the 0/2 building, with close collaborations with the VUmc-CCA. In addition to standard equipment, the following specialized facilities are present:
Embedding of Organ-on-Chip technology in research policy
- Organ on chip lab (Micronit and Fluigent microfluidic devices and pumps, flow sensors and control).
- Advanced tissue culture (oxygen ranges of 1-20%; state of the art skin and heart tissue engineering lab)
- 0|2Flow is the core flow cytometry facility within the 0/2 building. 02Flow aims at providing access to state-of-the-art technologies, services, and expertise in flow, flow-based imaging, and mass cytometry to enhance scientific discovery in fundamental and translational research. 0|2Flow is the most advanced flow cytometry facility in the Netherlands, equipped with state-of-the-art flow cytometry analyzers (BD Fortessa, BC Cyan), imaging flow cytometry (ISX-100), mass cytometry (CyTOF3-Helios) and sorters (MoFlo, BD AriaFusion, and BD Influx).
- Advanced microscopy core facility (AO|2M), which is a collaborative effort from the different pre-clinical departments from VUmc. AO|2M is equipped with confocal (Iive-cell; one- and two-photon) imaging; superresolution (STED) imaging; light-sheet imaging; wide field and electron microscopy. Expert operator support for internal and external users is provided by the AO|2M facility.
- Facilities are present for functional genomics siRNA screening, transcriptional genomies, proteomics mass-spec core facilities, peptide synthesis, and immunological ELISA, bead array and EliSpot read-outs.
Relevant (inter) national collaborations, in public and private sector
- - Micronit
- - Optics11
- - A-Skin
- - Phillips Research
- - LifeTec Group
- - TissUse (Berlin)
- - ACTA
- - VU
- - AMC
- - UvA
- - TU Delft
- - TU Berlin
- - Puget Sound Blood Center RI Seattle.
- Organ-on-chip technology within VUmc is embedded within three Research Institutes: VUmc Cancer Centre Amsterdam, Institute for Cardiovascular Research and MOVE as well as their sister VUmc-AMC alliance research institutes.
3 relevant key publications (PDF)- MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure. Kosten IJ, ...., Gibbs S. Toxicol Appl Pharmacol. 2015; 15;287(1):35-42.
- - Development, Validation, and Testing of a Human Tissue Engineered Hypertrophic Scar Model. van den Broek LJ,..., Gibbs S. ALTEX. 2012; 29(4):389-402.
- Long-Term Expansion in Platelet Lysate Increases Growth of Peripheral Blood-Derived Endothelial-Colony Forming Cells and Their Growth Factor-Induced Sprouting Capacity. L Tasev D, ...., Koolwijk P. PLoSOne. 2015 Jun 15;10(6):e0129935.chip
- - Comparison of the effects of a truncating and a missense MYBPC3 mutation on contractile parameters of engineered heart tissue. Wijnker PJM,...., van der Velden J, Carrier L. Journalof Molecular and Cellular Cardology 2016; 97:82-92.
3 relevant grants
- Human Immune Competent Skin-on-a-Chip to replace skin cancer animal experiments. Zon Mw MKMD. Gibbs,
de Gruijl, Dr A v/d Stolp (Phillips Research; Prof R Dekker (TU Delft / Phillips Research). 2013-2016
- Tissue Engineered Skin with human Hair follicles for human transplantation and In vitro skin-on-chip testing.
EuroStars. Gibbs VUMC / A-Skin / TU Berlin / TisUse GmbH Berlin.
- 'RECONNECT: Renal connection to microvascular disease and heart failure with preserved ejection fraction'
Other relevant information
A workgroup has been initiated on the VU campus to bring together scientists from different disciplines from VUmc (departments of Dermatology, Physiology, Medical Oncology, Molecular Cell Biology and Immunology), ACTA (research institute for Oral Regenerative Medicine) and VU (Laboratory for Myology) in order to generate awareness for hDMT. This workgroup will extend to AMC and Amsterdam Science park UvA.. The organ-on-a-chip initiative at the VUmc will be supported by a tight technology collaboration with the VU Departments of Physics and Analytical Chemistry, and the Laser lab Institute of the VU University Amsterdam, which can provide access to state-of-the-art imaging tools (including single molecule fluorescence imaging, high resolution deep tissue 2- and 3-photon imaging, Raman microscopy, opticaI coherence tomography, and atomic force microscopy), microfluidic systems, micromachined sensors (including force sensors for tissue and cell mechanical analysis), molecules to modulate and biosensors to monitor cell/organ function, and proteomics.