The impact of pericytes on the stability of microvascular networks in response to nanoparticles

Abstract Recapitulating the normal physiology of the microvasculature is pivotal in the development of more complex in-vitro models and organ-on-chip designs. Pericytes are an important component of the vasculature, promoting vessel stability, inhibiting vascular permeability and maintaining the vas...

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Main Authors: Matthew Dibble, Stefania Di Cio’, Piaopiao Luo, Frances Balkwill, Julien E. Gautrot
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-31352-x
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author Matthew Dibble
Stefania Di Cio’
Piaopiao Luo
Frances Balkwill
Julien E. Gautrot
author_facet Matthew Dibble
Stefania Di Cio’
Piaopiao Luo
Frances Balkwill
Julien E. Gautrot
author_sort Matthew Dibble
collection DOAJ
description Abstract Recapitulating the normal physiology of the microvasculature is pivotal in the development of more complex in-vitro models and organ-on-chip designs. Pericytes are an important component of the vasculature, promoting vessel stability, inhibiting vascular permeability and maintaining the vascular hierarchical architecture. The use of such co-culture for the testing of therapeutics and nanoparticle safety is increasingly considered for the validation of therapeutic strategies. This report presents the use of a microfluidic model for such applications. Interactions between endothelial cells and pericytes are first explored. We identify basal conditions required to form stable and reproducible endothelial networks. We then investigate interactions between endothelial cells and pericytes via direct co-culture. In our system, pericytes prevented vessel hyperplasia and maintained vessel length in prolonged culture (> 10 days). In addition, these vessels displayed barrier function and expression of junction markers associated with vessel maturation, including VE-cadherin, β-catenin and ZO-1. Furthermore, pericytes maintained vessel integrity following stress (nutrient starvation) and prevented vessel regression, in contrast to the striking dissociation of networks in endothelial monocultures. This response was also observed when endothelial/pericyte co-cultures were exposed to high concentrations of moderately toxic cationic nanoparticles used for gene delivery. This study highlights the importance of pericytes in protecting vascular networks from stress and external agents and their importance to the design of advanced in-vitro models, including for the testing of nanotoxicity, to better recapitulate physiological response and avoid false positives.
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spelling doaj.art-f0fc5020034345f5bdddfcf09c87d8202023-04-09T11:14:06ZengNature PortfolioScientific Reports2045-23222023-04-0113111310.1038/s41598-023-31352-xThe impact of pericytes on the stability of microvascular networks in response to nanoparticlesMatthew Dibble0Stefania Di Cio’1Piaopiao Luo2Frances Balkwill3Julien E. Gautrot4School of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of LondonSchool of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of LondonSchool of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of LondonSchool of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of LondonSchool of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of LondonAbstract Recapitulating the normal physiology of the microvasculature is pivotal in the development of more complex in-vitro models and organ-on-chip designs. Pericytes are an important component of the vasculature, promoting vessel stability, inhibiting vascular permeability and maintaining the vascular hierarchical architecture. The use of such co-culture for the testing of therapeutics and nanoparticle safety is increasingly considered for the validation of therapeutic strategies. This report presents the use of a microfluidic model for such applications. Interactions between endothelial cells and pericytes are first explored. We identify basal conditions required to form stable and reproducible endothelial networks. We then investigate interactions between endothelial cells and pericytes via direct co-culture. In our system, pericytes prevented vessel hyperplasia and maintained vessel length in prolonged culture (> 10 days). In addition, these vessels displayed barrier function and expression of junction markers associated with vessel maturation, including VE-cadherin, β-catenin and ZO-1. Furthermore, pericytes maintained vessel integrity following stress (nutrient starvation) and prevented vessel regression, in contrast to the striking dissociation of networks in endothelial monocultures. This response was also observed when endothelial/pericyte co-cultures were exposed to high concentrations of moderately toxic cationic nanoparticles used for gene delivery. This study highlights the importance of pericytes in protecting vascular networks from stress and external agents and their importance to the design of advanced in-vitro models, including for the testing of nanotoxicity, to better recapitulate physiological response and avoid false positives.https://doi.org/10.1038/s41598-023-31352-x
spellingShingle Matthew Dibble
Stefania Di Cio’
Piaopiao Luo
Frances Balkwill
Julien E. Gautrot
The impact of pericytes on the stability of microvascular networks in response to nanoparticles
Scientific Reports
title The impact of pericytes on the stability of microvascular networks in response to nanoparticles
title_full The impact of pericytes on the stability of microvascular networks in response to nanoparticles
title_fullStr The impact of pericytes on the stability of microvascular networks in response to nanoparticles
title_full_unstemmed The impact of pericytes on the stability of microvascular networks in response to nanoparticles
title_short The impact of pericytes on the stability of microvascular networks in response to nanoparticles
title_sort impact of pericytes on the stability of microvascular networks in response to nanoparticles
url https://doi.org/10.1038/s41598-023-31352-x
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