Characterization of gene expression changes in human neural stem cells and endothelial cells modeling a neurovascular microenvironment.
Brain-Derived Neurotrophic Factor
/ biosynthesis
Cell Line
Cellular Microenvironment
/ physiology
Coculture Techniques
Endothelial Cells
/ metabolism
Fibroblast Growth Factors
/ biosynthesis
Gene Expression
Humans
Microvessels
/ cytology
Neural Stem Cells
/ metabolism
Neurovascular Coupling
/ physiology
Angiogenesis
Basement membrane
Endothelial cell
Extracellular matrix
Neural stem cell
Neurovascular unit
Journal
Brain research bulletin
ISSN: 1873-2747
Titre abrégé: Brain Res Bull
Pays: United States
ID NLM: 7605818
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
26
12
2019
revised:
12
02
2020
accepted:
19
02
2020
pubmed:
25
2
2020
medline:
1
9
2021
entrez:
25
2
2020
Statut:
ppublish
Résumé
Angiogenesis-mediated neovascularization correlates with recovery after intracerebral implantation of neural stem cells (NSCs) in stroke. To elucidate NSCs' mechanism of action, it is essential to understand how these interact with the brain's vasculature after implantation. Using an all-human endothelial cell (EC, D3 cell line) and NSC (STROC05 and CTXOE03) co-culture model, fluorescently activated cell sorting (FACS) was used to isolate each cell type for a comparison of gene expression between monocultures of undifferentiated proliferating and differentiated non-proliferating cells. Gene expression for angiogenic factors (vascular endothelial growth factor, platelet derived growth factor, angiopoietin), as well as cell survival (brain derived neurotrophic factor, fibroblast growth factor) and migration (stromal cell-derived factor-1a) were measured and contrasted with the corresponding receptors on each cell type. The cellular source of extracellular matrix defining the basement membrane (vitronectin, fibronectin, laminin, collagen I and IV) and neuropil (hyaluronic acid, aggrecan, neurocan, thrombospondin, nidogen and brain associated link protein-1) was evaluated for NSCs and ECs. Co-culturing dramatically changed the expression profiles of each cell type in comparison to undifferentiated, but also differentiated cells. These results indicate that monocultures provide a poor model to investigate the cellular signaling involved in a tissue repair response. Co-cultures of NSCs and ECs forming vasculature-like structures (VLS) provide a more complex model to investigate NSC-induced neovascularization. These in vitro studies are essential to tease out individual cell signaling in NSCs and ECs to develop a mechanistic understanding of the efficacy of NSCs as a therapeutic for stroke.
Identifiants
pubmed: 32092433
pii: S0361-9230(19)31050-0
doi: 10.1016/j.brainresbull.2020.02.008
pmc: PMC7103513
mid: NIHMS1571377
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9-19Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/D014808/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS082226
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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