Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips

Scientific Reports, vol. 11, pp. 2281

Abstract

In vitro neuronal models are essential for studying neurological physiology, disease mechanisms and potential treatments. Most in vitro models lack controlled vasculature, despite its necessity in brain physiology and disease. Organ-on-chip models offer microfluidic culture systems with dedicated micro-compartments for neurons and vascular cells. Such multi-cell type organs-on-chips can emulate neurovascular unit (NVU) physiology, however there is a lack of systematic data on how individual cell types are affected by culturing on microfluidic systems versus conventional culture plates. This information can provide perspective on initial findings of studies using organs-on-chip models, and further optimizes these models in terms of cellular maturity and neurovascular physiology. Here, we analysed the transcriptomic profiles of co-cultures of human induced pluripotent stem cell (hiPSC)-derived neurons and rat astrocytes, as well as one-day monocultures of human endothelial cells, cultured on microfluidic chips. For each cell type, large gene expression changes were observed when cultured on microfluidic chips compared to conventional culture plates. Endothelial cells showed decreased cell division, neurons and astrocytes exhibited increased cell adhesion, and neurons showed increased maturity when cultured on a microfluidic chip. Our results demonstrate that culturing NVU cell types on microfluidic chips changes their gene expression profiles, presumably due to distinct surface-to-volume ratios and substrate materials. These findings inform further NVU organ-on-chip model optimization and support their future application in disease studies and drug testing.

Authors 10

1. Heleen H. T. Middelkamp corresponding

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands. h.h.t.middelkamp@utwente.nl

   BIOS/Lab on a Chip, University of Twente, Enschede, The Netherlands. h.h.t.middelkamp@utwente.nl

   Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands

2. Anouk H. A. Verboven corresponding

   Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Centre for Molecular and Biomolecular Informatics, Radboudumc, Radboud Institute for Molecular Life Sciences, 6500 HB, Nijmegen, The Netherlands. Anouk.Verboven@radboudumc.nl

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands. Anouk.Verboven@radboudumc.nl

   Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. Anouk.Verboven@radboudumc.nl

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands

3. Aisen Vivas

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands

   BIOS/Lab on a Chip, University of Twente, Enschede, The Netherlands

4. Chantal Schoenmaker

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands

5. Teun M. Klein Gunnewiek

   Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands

   Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands

6. Robert C. J. J. Passier Aachen Department of Anatomy and Embryology

   Leiden University · Leiden University Medical Center · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands

   Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, The Netherlands

7. Cornelis A. Albers

   Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands

   Department of Molecular Developmental Biology, Radboud University, Nijmegen, The Netherlands

   Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands

8. Peter A.C. ’t Hoen

   Radboud University Medical Center · Radboud Institute for Molecular Life Sciences

   Affiliation as printed

   Centre for Molecular and Biomolecular Informatics, Radboudumc, Radboud Institute for Molecular Life Sciences, 6500 HB, Nijmegen, The Netherlands

9. Nael Nadif Kasri

   Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Cognitive Neurosciences, Radboudumc, Nijmegen, The Netherlands

   Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands

   Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands

10. Andries D. van der Meer corresponding

    University of Twente

    Affiliation as printed

    Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands. andries.vandermeer@utwente.nl

    Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands