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

Title: Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection
Authors: Claire H. Masterson; Arata Tabuchi; Grace Hogan; Glenn Fitzpatrick; Steven W. Kerrigan; Mirjana Jerkic; Wolfgang M. Kuebler; John G. Laffey; Gerard F. Curley
Source: Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
Publisher Information: Nature Portfolio, 2021.
Publication Year: 2021
Collection: LCC:Medicine; LCC:Science
Subject Terms: Medicine; Science
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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-021-83894-7
Access URL: https://doaj.org/article/79bc632af6ef4beaa0c8151bdb5bc75e
Accession Number: edsdoj.79bc632af6ef4beaa0c8151bdb5bc75e
Database: Directory of Open Access Journals