PMID- 34804595
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231102
IS  - 2059-6553 (Electronic)
IS  - 2059-6553 (Linking)
VI  - 5
IP  - 4
DP  - 2021 Dec
TI  - 3D hydrogel models of the neurovascular unit to investigate blood-brain barrier 
      dysfunction.
PG  - NS20210027
LID - 10.1042/NS20210027 [doi]
LID - NS20210027
AB  - The neurovascular unit (NVU), consisting of neurons, glial cells, vascular cells 
      (endothelial cells, pericytes and vascular smooth muscle cells (VSMCs)) together 
      with the surrounding extracellular matrix (ECM), is an important interface 
      between the peripheral blood and the brain parenchyma. Disruption of the NVU 
      impacts on blood-brain barrier (BBB) regulation and underlies the development and 
      pathology of multiple neurological disorders, including stroke and Alzheimer's 
      disease (AD). The ability to differentiate induced pluripotent stem cells (iPSCs) 
      into the different cell types of the NVU and incorporate them into physical 
      models provides a reverse engineering approach to generate human NVU models to 
      study BBB function. To recapitulate the in vivo situation such NVU models must 
      also incorporate the ECM to provide a 3D environment with appropriate mechanical 
      and biochemical cues for the cells of the NVU. In this review, we provide an 
      overview of the cells of the NVU and the surrounding ECM, before discussing the 
      characteristics (stiffness, functionality and porosity) required of hydrogels to 
      mimic the ECM when incorporated into in vitro NVU models. We summarise the 
      approaches available to measure BBB functionality and present the techniques in 
      use to develop robust and translatable models of the NVU, including transwell 
      models, hydrogel models, 3D-bioprinting, microfluidic models and organoids. The 
      incorporation of iPSCs either without or with disease-specific genetic mutations 
      into these NVU models provides a platform in which to study normal and disease 
      mechanisms, test BBB permeability to drugs, screen for new therapeutic targets 
      and drugs or to design cell-based therapies.
CI  - (c) 2021 The Author(s).
FAU - Potjewyd, Geoffrey
AU  - Potjewyd G
AD  - Division of Neuroscience and Experimental Psychology, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Manchester M13 9PT, U.K.
FAU - Kellett, Katherine A B
AU  - Kellett KAB
AD  - Division of Neuroscience and Experimental Psychology, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Manchester M13 9PT, U.K.
FAU - Hooper, Nigel M
AU  - Hooper NM
AUID- ORCID: 0000-0002-5811-3484
AD  - Division of Neuroscience and Experimental Psychology, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Manchester M13 9PT, U.K.
AD  - Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science 
      Centre, Northern Care Alliance and University of Manchester, Manchester, U.K.
LA  - eng
GR  - MR/L023784/2/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20211109
PL  - England
TA  - Neuronal Signal
JT  - Neuronal signaling
JID - 101721079
PMC - PMC8579151
OTO - NOTNLM
OT  - blood brain barrier
OT  - extracellular matrix
OT  - induced pluripotent stem cells
OT  - neurodegeneration
OT  - stroke
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2021/11/23 06:00
MHDA- 2021/11/23 06:01
PMCR- 2021/11/09
CRDT- 2021/11/22 06:47
PHST- 2021/08/16 00:00 [received]
PHST- 2021/10/20 00:00 [revised]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/22 06:47 [entrez]
PHST- 2021/11/23 06:00 [pubmed]
PHST- 2021/11/23 06:01 [medline]
PHST- 2021/11/09 00:00 [pmc-release]
AID - NS20210027 [pii]
AID - 10.1042/NS20210027 [doi]
PST - epublish
SO  - Neuronal Signal. 2021 Nov 9;5(4):NS20210027. doi: 10.1042/NS20210027. eCollection 
      2021 Dec.