Vrije Universiteit Amsterdam ‐ structure, expertise and facilities relevant for Organ‐on‐Chip technology
VU Amsterdam boasts 3 faculties, Faculty of Sciences (FS), Faculty of Behavioural and Movement Sciences (FGB) and the Acadamic Centre of Dentistry of Amsterdam (ACTA), in which Organ‐on‐Chip technology is developed and applied. These faculties host the following labs/departments with expert facilities and expertise.
ACTA ‐ Department of Oral Cell Biology
Models: Joint‐on‐Chip, Bone‐on‐Chip and Broken‐Bone‐on‐Chip Researchers: Prof. dr. Jenneke Klein‐Nulend and Dr. Astrid Bakker Bone is highly mechanosensitive tissue and mechanical loading is a strong stimulus for bone
remodelling and osteogenesis. Mechanical loading has a direct on effect on cellular responses by cellular and nuclear deformation as well an indirect effect by modulation of the expression of growth factors and cytokines. Based on a long record of research into mechanotransduction this group is currently working on 3 organ‐on‐Chip models which include different cell types and physico‐chemical cues.
Facilities: ML1 and ML2 cell culture labs with experimental equipment to apply fluid shear stress,cyclic tensile stretch and pressure.
Bonafide – Eurostars: Bone‐on‐Chip Analysis Platform for In Vitro Drug Performance Evaluation (PI Bakker AD)
mechanoCHIP‐ Eurostars: Osteosarcoma‐on‐Chip platform integrated with mechanical loading (PI Bakker)
van Santen, V. J. B., Bastidas Coral, A. P., Hogervorst, J. M. A., Klein‐Nulend, J. & Bakker, A. D. Biologically Relevant In Vitro 3D‐Model to Study Bone Regeneration Potential of Human Adipose Stem Cells. Biomolecules 12, doi:10.3390/biom12020169 (2022).
Researchers: Prof. dr. Sue Gibbs and Prof. Floris Bikker. Our mouth is inhabited by abundant microbes which continuously interact with the soft tissues within our mouth such as our oral mucosa (gingiva). Such mucosa‐microbe interactions play important roles in oral health and disease. Also, we often have dental implants or fillings to replace or repair our damaged teeth. In the lab we have engineered pieces of living oral mucosa in 3D which consists of a reconstructed gingiva epithelium containing Langerhans Cells on a fibroblast populated hydrogel. This organotypic gingiva is used to investigate interactions with healthy and pathogenic microbes and also to investigate potential adverse effects caused by materials contained within implants and fillings. Systemic immune responses are investigated using OoC technology (TissUse).
Facilities: specialized ML2 culture facility with TissUse OoC consul; ML2 microbiology facility; biomaterials facility. Collaborations, in public and private sector: TissUse, Micronit, Biolamina, CELLINK, Amsterdam UMC (VUMC),
Project title: BodyBarriers: A novel mucosa‐blood‐brain organ‐on‐chip platform for the safety testing of medical devices type of grant: TTW (2022‐2026) – 855k€, Partners: ACTA, Amsterdam UMC VUMC, 3/6
TissUse, Mimetas, Biolamina, project leader: Prof S. Gibbs, coapplicants: Prof. A Feilzer, Prof E de Vries, Dr V Heine.
Project title: FUNC‐BIOINK, Functionized collagen for bioprinting. type of grant: EuroStars (2019‐ 2022). finance: € 455.000 cash for ACTA (total project = €1.9M of which 50% is matching)
Shang, L., et al., Commensal and Pathogenic Biofilms Alter Toll‐Like Receptor Signaling in Reconstructed Human Gingiva. Front Cell Infect Microbiol, 2019. 9: p. 282
Faculty of Behavioural and Movement Sciences
Models: 2D myotube and muscle stem cell models with integrated mechanical loading devices Researchers: Prof. dr. Richard Jaspers and Dr. Rob Wüst
Muscle function is largely determined by myofiber size and oxidative capacity. We aim to uncover optimal physico‐chemical cues for myogenesis, adapation of myofiber size as well as mitochondrial biosynthesis and function. Our current models are currently 2D, but we would like to collaborate with hDMT partners to further develop 3D models.
- Identify the role and synergistic effects of growth factors and cytokines
- Oxidative metabolism and myofiber size are inversely related and hypetrophy and mitochondrial biosynthesis are mutually exclusive. We investigate the role of oxygen diffusion on the anabolic potential of myofibers and how oxygen supply can be improved by angiogenesis
- The extracellular matrix is a scaffold for myofibers which binds and sequester growth factors and cytokines but also plays a role in myofascial force transmission. Effects of tensile stress, shear forces and pressure are tested for their effects on protein synthesis in both radial and longitudinal myofiber direction.
- Muscle regeneration relies on the adequate activation and differentiation of muscle stem cells. We have recently shown that mechanical loading of these cells in their native niche on top of their host myofiber are sensitive to shear loading triggering their proliferation.
Relevant collaborations in public and private sector: Optics11, Lumicks, Ipsen
Erasmus Mundes joint doctorate programme MOVE‐AGE.
Haroon M, Klein‐Nulend J, Bakker AD, Jin J, Seddiqi H, Offringa C, de Wit GMJ, Le Grand F, Giordani L,Liu KJ, Knight RD & Jaspers RT. (2021). Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche. Biophys J 120, 2665‐2678.
Haroon M, Boers HE, Bakker AD, Bloks NGC, Hoogaars WMH, Giordani L, Musters RJP, Deldicque L,Koppo K, Le Grand F, Klein‐Nulend J & Jaspers RT. (2022). Reduced growth rate of aged muscle stem cells is associated with impaired mechanosensitivity. Aging 14, 28‐53
Faculty of Sciences ‐ Center for Neurogenomics and Cognitive Research
Model: brain‐on‐chip model
The CNRN is an expertise center at the Vrije Universiteit Amsterdam with over 150 researchers and 20 research teams. The CNCR has the mission to understand the mechanisms underlying brain function and dysfunction, providing new perspectives on diagnosis and treatment of brain diseases. The human iPSC technologies are increasingly implemented in the different CNCR research programs. The brain‐ on‐chip models are benefiting from CNCR’s leading experts in brain research from molecular to functional analysis, thereby validating, optimizing and making these systems more physiological relevant.
ZonMW PSIDER “BRAINMODEL” (4 million euro; coordinator Prof. dr. Matthijs Verhage)Participant in the Human Brain Project, a European Commission Future and Emerging Technologies. (FET) Flagship that was awarded 1 Billion Euro in 2013 (Prof. dr Huib Mansvelder & Dr. Christiaan de Kock).
Gravitation grant BRAINSCAPES (20 million euro; coordinator Prof. dr Danielle Posthuma; co‐applicant Prof. dr. Guus Smit & Prof. dr. Huib Mansvelder).
Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Trubetskoy V, … Verhage M,… Posthuma D… Schizophrenia Working Group of the Psychiatric Genomics Consortium. Nature. 2022 Apr;604(7906):502‐508.
Human neocortical expansion involves glutamatergic neuron diversification. Berg J, …, de Kock CPJ, Mansvelder HD, Tamas G, Zeng H, Koch C, Lein ES. Nature. 2021 Oct;598(7879):151‐158.
SynGO: An Evidence‐Based, Expert‐Curated Knowledge Base for the Synapse. Koopmans F,… Smit AB, Verhage M. Neuron. 2019 Jul 17;103(2):217‐234.e4.
A Single‐Cell Model for Synaptic Transmission and Plasticity in Human iPSC‐Derived Neurons. MeijerM, …, Brüstle O, Verhage M. Cell Rep. 2019 May 14;27(7):2199‐2211.e6.
Differential Maturation of the Two Regulated Secretory Pathways in Human iPSC‐Derived Neurons.Emperador Melero J, …, Verhage M. Stem Cell Reports. 2017 Mar 14;8(3):659‐672.
Genetically‐Informed Patient Selection for iPSC Studies of Complex Diseases May Aid in Reducing Cellular Heterogeneity. Hoekstra SD, Stringer S, Heine VM, Posthuma D. Front Cell Neurosci. 2017 Jun 13;11:164.
Modeling psychiatric disorders: from genomic findings to cellular phenotypes. Falk A, … Posthuma D, Djurovic S. Mol Psychiatry. 2016 Sep;21(9):1167‐79
Faculty of Sciences ‐ Department of Chemistry and Pharmaceutical Sciences
Models: System biology models, Analytical and computational
Researcher: Prof. dr. Bas Teusink
Develop and apply a systems biology workflow to design cell culture media that are fully chemically defined, truly animal‐free (no foetal calf serum) and are tailored to their purpose (fit‐for‐purpose)
In the field of microbiology, advances in bioinformatics and systems biology have made systematic and rational design of chemically defined media possible. It is based on the integration of omics data into so‐called genome‐scale metabolic models that simulate growth on the basis of nutrient inputs
and biomass requirements.
Development of defined and fit‐for purpose culture media can provide huge benefits:
No cross immunology
Chemically defined media for good manufacturing practice (GMP) and down‐stream processing
Control over nutritional, hormonal and growth factor needs and metabolic status
Unique data collection for insight in role of growth medium composition on cell physiology
Vici Grant 2015
Elsemman IE, Rodriguez Prado A, Grigaitis P, Garcia Albornoz M, Harman V, Holman SW, van Heerden J, Bruggeman FJ, Bisschops MMM, Sonnenschein N, Hubbard S, Beynon R, Daran‐Lapujade P, Nielsen J & Teusink B. (2022).Whole‐cell modeling in yeast predicts compartment‐specific proteome constraints that drive metabolic strategies. Nat Commun 13, 801.
Nilsson A, Haanstra JR, Engqvist M, Gerding A, Bakker BM, Klingmüller U, Teusink B & Nielsen J.(2020). Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis. Proc Natl Acad Sci U S A 117, 10294‐10304