PMID- 33500551
OWN - NLM
STAT- MEDLINE
DCOM- 20210915
LR  - 20240330
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jan 26
TI  - Cell type-specific changes in transcriptomic profiles of endothelial cells, 
      iPSC-derived neurons and astrocytes cultured on microfluidic chips.
PG  - 2281
LID - 10.1038/s41598-021-81933-x [doi]
LID - 2281
AB  - 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.
FAU - Middelkamp, H H T
AU  - Middelkamp HHT
AD  - Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands. 
      h.h.t.middelkamp@utwente.nl.
AD  - BIOS/Lab on a Chip, University of Twente, Enschede, The Netherlands. 
      h.h.t.middelkamp@utwente.nl.
FAU - Verboven, A H A
AU  - Verboven AHA
AD  - Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands. 
      Anouk.Verboven@radboudumc.nl.
AD  - Donders Institute for Brain, Cognition and Behaviour, Radboud University, 
      Nijmegen, The Netherlands. Anouk.Verboven@radboudumc.nl.
AD  - Centre for Molecular and Biomolecular Informatics, Radboudumc, Radboud Institute 
      for Molecular Life Sciences, 6500 HB, Nijmegen, The Netherlands. 
      Anouk.Verboven@radboudumc.nl.
FAU - De Sa Vivas, A G
AU  - De Sa Vivas AG
AD  - Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands.
AD  - BIOS/Lab on a Chip, University of Twente, Enschede, The Netherlands.
FAU - Schoenmaker, C
AU  - Schoenmaker C
AD  - Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.
FAU - Klein Gunnewiek, T M
AU  - Klein Gunnewiek TM
AD  - Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.
AD  - Donders Institute for Brain, Cognition and Behaviour, Radboud University, 
      Nijmegen, The Netherlands.
FAU - Passier, R
AU  - Passier R
AD  - Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands.
AD  - Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, 
      The Netherlands.
FAU - Albers, C A
AU  - Albers CA
AD  - Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.
AD  - Donders Institute for Brain, Cognition and Behaviour, Radboud University, 
      Nijmegen, The Netherlands.
AD  - Department of Molecular Developmental Biology, Radboud University, Nijmegen, The 
      Netherlands.
FAU - 't Hoen, P A C
AU  - 't Hoen PAC
AD  - Centre for Molecular and Biomolecular Informatics, Radboudumc, Radboud Institute 
      for Molecular Life Sciences, 6500 HB, Nijmegen, The Netherlands.
FAU - Nadif Kasri, N
AU  - Nadif Kasri N
AD  - Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands.
AD  - Department of Cognitive Neurosciences, Radboudumc, Nijmegen, The Netherlands.
AD  - Donders Institute for Brain, Cognition and Behaviour, Radboud University, 
      Nijmegen, The Netherlands.
FAU - van der Meer, A D
AU  - van der Meer AD
AD  - Applied Stem Cell Technologies, University of Twente, Enschede, The Netherlands. 
      andries.vandermeer@utwente.nl.
LA  - eng
GR  - 91217055/ZONMW_/ZonMw/Netherlands
GR  - 024.003.001/NWO gravitation/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210126
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Cell Adhesion/genetics
MH  - Cell Differentiation/genetics
MH  - Cells, Cultured
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Gene Ontology
MH  - Human Umbilical Vein Endothelial Cells/*metabolism
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*cytology
MH  - *Microfluidics
MH  - Neurons/cytology/*metabolism
MH  - Rats
MH  - Transcriptome/*genetics
PMC - PMC7838281
COIS- The authors declare no competing interests.
EDAT- 2021/01/28 06:00
MHDA- 2021/09/16 06:00
PMCR- 2021/01/26
CRDT- 2021/01/27 05:49
PHST- 2020/07/16 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/01/27 05:49 [entrez]
PHST- 2021/01/28 06:00 [pubmed]
PHST- 2021/09/16 06:00 [medline]
PHST- 2021/01/26 00:00 [pmc-release]
AID - 10.1038/s41598-021-81933-x [pii]
AID - 81933 [pii]
AID - 10.1038/s41598-021-81933-x [doi]
PST - epublish
SO  - Sci Rep. 2021 Jan 26;11(1):2281. doi: 10.1038/s41598-021-81933-x.