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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Format: | Article |
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Nature Portfolio
2023-04-01
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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. |
first_indexed | 2024-04-09T18:55:30Z |
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id | doaj.art-f0fc5020034345f5bdddfcf09c87d820 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-04-09T18:55:30Z |
publishDate | 2023-04-01 |
publisher | Nature Portfolio |
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series | Scientific Reports |
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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