Intra-vital imaging of mesenchymal stromal cell.....pdf (2.46 MB)

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

Download (2.46 MB)
journal contribution
posted on 01.07.2021, 15:51 by Claire H Masterson, Arata Tabuchi, Grace Hogan, Glenn Fitzpatrick, Steven Kerrigan, Mirjana Jerkic, Wolfgang M Kuebler, John G Laffey, Gerard Curley
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.

Funding

Canadian Institute of Health Research

Government of Ontario, Ministry of Research and Innovation, Early Researcher Award

University of Toronto Department of Anaesthesia Merit Award & Clinical Scientist Transition Award

International Anesthesia Research Society

Canadian Anaesthesiology Society

History

Comments

The original article is available at https://www.nature.com

Published Citation

Masterson CH, Tabuchi A, Hogan G, Fitzpatrick G, Kerrigan SW, Jerkic M, Kuebler WM, Laffey JG, Curley GF. Intra-vital imaging of mesenchymal stromal cell kinetics in the pulmonary vasculature during infection. Sci Rep. 2021;11(1):5265.

Publication Date

4 March 2021

PubMed ID

33664277

Department/Unit

  • Anaesthetics and Critical Care
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology
  • Immunity, Infection and Inflammation
  • Biomaterials and Regenerative Medicine

Publisher

Nature Publishing Group

Version

  • Published Version (Version of Record)