Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection

Abstract Mesenchymal stem/stromal cells (MSCs) have demonstrated efficacy in pre-clinical models of inflammation and tissue injury, including in models of lung injury and infection. Rolling, adhesion and transmigration of MSCs appears to play a role during MSC kinetics in the systemic vasculature. H...

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Autores principales:	Claire H. Masterson, Arata Tabuchi, Grace Hogan, Glenn Fitzpatrick, Steven W. Kerrigan, Mirjana Jerkic, Wolfgang M. Kuebler, John G. Laffey, Gerard F. Curley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/79bc632af6ef4beaa0c8151bdb5bc75e
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spelling	oai:doaj.org-article:79bc632af6ef4beaa0c8151bdb5bc75e2021-12-02T11:37:25ZIntra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection10.1038/s41598-021-83894-72045-2322https://doaj.org/article/79bc632af6ef4beaa0c8151bdb5bc75e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83894-7https://doaj.org/toc/2045-2322Abstract Mesenchymal stem/stromal cells (MSCs) have demonstrated efficacy in pre-clinical models of inflammation and tissue injury, including in models of lung injury and infection. Rolling, adhesion and transmigration of MSCs appears to play a role during MSC kinetics in the systemic vasculature. However, a large proportion of MSCs become entrapped within the lungs after intravenous administration, while the initial kinetics and the site of arrest of MSCs in the pulmonary vasculature are unknown. We examined the kinetics of intravascularly administered MSCs in the pulmonary vasculature using a microfluidic system in vitro and intra-vital microscopy of intact mouse lung. In vitro, MSCs bound to endothelium under static conditions but not under laminar flow. VCAM-1 antibodies did not affect MSC binding. Intravital microscopy demonstrated MSC arrest at pulmonary micro-vessel bifurcations due to size obstruction. Retention of MSCs in the pulmonary microvasculature was increased in Escherichia coli-infected animals. Trapped MSCs deformed over time and appeared to release microvesicles. Labelled MSCs retained therapeutic efficacy against pneumonia. Our results suggest that MSCs are physically obstructed in pulmonary vasculature and do not display properties of rolling/adhesion, while retention of MSCs in the infected lung may require receptor interaction.Claire H. MastersonArata TabuchiGrace HoganGlenn FitzpatrickSteven W. KerriganMirjana JerkicWolfgang M. KueblerJohn G. LaffeyGerard F. CurleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claire H. Masterson Arata Tabuchi Grace Hogan Glenn Fitzpatrick Steven W. Kerrigan Mirjana Jerkic Wolfgang M. Kuebler John G. Laffey Gerard F. Curley Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
description	Abstract Mesenchymal stem/stromal cells (MSCs) have demonstrated efficacy in pre-clinical models of inflammation and tissue injury, including in models of lung injury and infection. Rolling, adhesion and transmigration of MSCs appears to play a role during MSC kinetics in the systemic vasculature. However, a large proportion of MSCs become entrapped within the lungs after intravenous administration, while the initial kinetics and the site of arrest of MSCs in the pulmonary vasculature are unknown. We examined the kinetics of intravascularly administered MSCs in the pulmonary vasculature using a microfluidic system in vitro and intra-vital microscopy of intact mouse lung. In vitro, MSCs bound to endothelium under static conditions but not under laminar flow. VCAM-1 antibodies did not affect MSC binding. Intravital microscopy demonstrated MSC arrest at pulmonary micro-vessel bifurcations due to size obstruction. Retention of MSCs in the pulmonary microvasculature was increased in Escherichia coli-infected animals. Trapped MSCs deformed over time and appeared to release microvesicles. Labelled MSCs retained therapeutic efficacy against pneumonia. Our results suggest that MSCs are physically obstructed in pulmonary vasculature and do not display properties of rolling/adhesion, while retention of MSCs in the infected lung may require receptor interaction.
format	article
author	Claire H. Masterson Arata Tabuchi Grace Hogan Glenn Fitzpatrick Steven W. Kerrigan Mirjana Jerkic Wolfgang M. Kuebler John G. Laffey Gerard F. Curley
author_facet	Claire H. Masterson Arata Tabuchi Grace Hogan Glenn Fitzpatrick Steven W. Kerrigan Mirjana Jerkic Wolfgang M. Kuebler John G. Laffey Gerard F. Curley
author_sort	Claire H. Masterson
title	Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
title_short	Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
title_full	Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
title_fullStr	Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
title_full_unstemmed	Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
title_sort	intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/79bc632af6ef4beaa0c8151bdb5bc75e
work_keys_str_mv	AT clairehmasterson intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT aratatabuchi intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT gracehogan intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT glennfitzpatrick intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT stevenwkerrigan intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT mirjanajerkic intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT wolfgangmkuebler intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT johnglaffey intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection AT gerardfcurley intravitalimagingofmesenchymalstromalcellkineticsinthepulmonaryvasculatureduringinfection
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Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection

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