Radboud university medical center

Researchers of the Radboud university medical center (Radboudumc) focus on today’s scientific health challenges as well as keeping an eye on emerging diseases of the future. With the mission ‘to have a significant impact on healthcare’ and a strategic focus on personalized healthcare through ‘the patient as partner’, the core activities of patient health care, research and education are bundled in 17 disease-oriented research themes in which fundamental researchers and clinicians meet regularly and integrate their knowledge and expertise to realize important improvements in patient-directed science, diagnosis and treatment. The disease-oriented research themes include cancer development, rare cancers, digestive tract, urological and women’s cancers, infectious, inflammatory, mitochondrial and alzheimer’s diseases, renal, sensory, neurodevelopment and stress-related disorders, and vascular damage. Radboudumc consists of 11.000 colleagues, 50 departments, 3000 students and 1000 beds.

Expertise relevant for Organ-on-Chip technology:

  • Construction and in vitro/pre-clinical evaluation of cell-grown bioscaffolds with extracellular matrix molecules and bio-actives; Biochemical methods for the analysis of matrix molecules
  • Design of photomasks, fabrication of masters/replica to generate multi-layered PDMS Organ-on-Chip devices
  • Growth and differentiation of iPSCs and rodent/patient’s primary cells from urine, organs and tumor tissue (renal, heart, skeletal muscle, neurons, skin, retina) in Ussing chambers/3D matrix systems/Organ-on-Chip devices/micro-electrode arrays [MEAs of brain cells]
  • Transmembrane and transcellular electrolyte transport assays through polarized epithelial cells
  • Transcriptomics, and cellular/fluid/urine proteomics, glycomics and metabolomics
  • Cell transfection and gene/mRNA editing (siRNA/CRISPR-Cas9) techniques
  • Advanced quantitative in vitro and in vivo (rodents) quantitative bio-imaging
  • Drug delivery and efficacy measurements in tumor-on-chip devices
  • Knowledge for in vivo validation of model systems (kidney, retina, adrenal gland, brain)

Embedding Organ-on-Chip technology in research policy

For many themes, the Organ-on-Chip technology forms the interphase between molecular studies and physiological studies in patients. Therefore, the Stem Cell and Differentiation Technology Center has been set up and is sponsored by the department of Human Genetics and Radboudumc. In the human movement theme, all projects involve the use of Brain on Chip technology in which neuronal networks of individual patients are phenotyped with the ultimate aim to perform drug screening for individual patients rather that disease specific, i.e. getting to personalized medicine. To increase Organ-on-Chip research and collaboration with the UTwente, the Radboudumc and UTwente provided 4 collaborative TURBO grants.

News

Added value hDMT

  • Access to large cohorts of patients with disorders in the theme fields indicated above
  • Access to the indicated facilities, e.g. patient derived iPSCs and differentiated cell types
  • Interaction with and access to efficient fundamental-clinical research teams with extensive knowledge on the indicated themes
  • New collaborations with Organ-on-Chip researchers with the above expertises

Added value for Radboudumc

  • Access to knowledge and academic-industry networks
  • Access to state-of-the art developments in Organ-on-Chip devices and sensors
  • Possibility for applying for consortium grants
  • Exchange of differentiation protocols for iPSCs
  • Access to equipment not available at Radboudumc

Facilities relevant for Organ-on-Chip technology:

  • Lyophilisators for preparation of scaffolds; apparatuses to homogenise native matrices (pulverisette, specific blenders)
  • MLI/II laboratories for cell differentiation and transfection experiments
  • Flow chambers, electrophysiological/patch clamp analysis, radiotracer transport studies
  • Technology centers on genomics, mass-spectrometry, bio-informatics, flow cytometry, translational neuroscience
  • Stem Cell and differentiation Technology Center
  • PRIME preclinical Imaging Center (MRI, SPECT, PET optical imaging, intrinsic optical and multiphoton microscopy, ultrasound and photoacoustic imaging; cognition and behaviour rooms for rodents) 
  • Microscopic imaging center (super-resolution microscopy, time-lapse confocal microscopy, electron microscopy, correlative light-electron microscopy, intravital multi-photon excitation microscopy)
  • RadboudUMC biobank (standardized collection of clinical samples with detailed clinical data) 
  • Access to primary patient material

Relevant (inter)national collaborations

Public sector: Prof. Huck (Nijmegen); Profs. M. Verhaar, H. Clevers (Utrecht); Prof. D. Stamatialis, A. van der Meer, Severine le Gac (TU Twente); Pijnappel (Erasmus MC); Rabelink (LUMC); Prof. Davies (Edinburgh); Prof. Eiges (Jerusalem, Israel).

Patient organisations: K.I.D.S. IQ Project (Canada), Koolen-de Vries syndrome foundation (US), Epilepsie Vereniging Nederland.

Private sector: Roche.

 

Publications

  • Tegtmeyer L et al., Multiple phenotypes in phosphoglucomutase 1 deficiency. New Eng J Med, 2014; 370(6):533-42. Read
  • Frega M et al., Rapid Neuronal Differentiation of Induced Pluripotent Stem Cells for Measuring Network Activity on Micro-electrode Arrays. JoVE, no. 119, Jan. 2017. Read
  • Meddens MBM et al., Actomyosin-dependent dynamic spatial pattern of cytoskeletal components drive mesoscale podosome organization. Nat Commun. 2016, 7:13127. Read

Relevant grants

A novel generation of skin substitutes to clinically treat a broad spectrum of severe skin defects. 2011-2017 EU FP7 Health 5996. 9 European partners. 6000 kEuro

Brain on a dish: development of innovative stem cell technologies for personalized medicine in epilepsy. NWO ZonMW Top PI: H. van Bokhoven, N. Nadif Kasri (Radboudumc), Judith  Verhoeven, Jurgen Schelhaas (Kempenhaeghe Heeze), 675 kEuro.

EYE-RISK; Exploring the combined roles of genetic and non-genetic factors for developing agerelated macular degeneration: A systems level analysis of disease subgroups, risk factors, and pathways. European Union. Coordinators: M. Ueffing & C. Klaver, 2015-2019, 5.972 kEuro.