1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs’ effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.

          Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.

          Methods: Human monocyte–derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.

          Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker expression, and augmented phagocytic capacity of human MDMs stimulated with LPS or ARDS BALF. These effects were partially mediated by CD44-expressing EVs. Adoptive transfer of AMs pretreated with MSC-derived EVs reduced inflammation and lung injury in LPS-injured mice. Inhibition of oxidative phosphorylation in MDMs prevented the modulatory effects of MSCs. Generating dysfunctional mitochondria in MSCs using rhodamine 6G pretreatment also abrogated these effects.

          Conclusions: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV-mediated mitochondrial transfer. MSC-induced changes in macrophage phenotype critically depend on enhancement of macrophage oxidative phosphorylation. AMs treated with MSC-derived EVs ameliorate lung injury in vivo.

          Related collections

          Author and article information

          Journal
          Am J Respir Crit Care Med
          Am. J. Respir. Crit. Care Med
          ajrccm
          American Journal of Respiratory and Critical Care Medicine
          American Thoracic Society
          1073-449X
          1535-4970
          15 November 2017
          15 November 2017
          15 November 2017
          15 May 2018
          : 196
          : 10
          : 1275-1286
          Affiliations
          Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom
          Author notes
          Correspondence and requests for reprints should be addressed to Anna D. Krasnodembskaya, B.Sc., M.Sc., Ph.D., Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. E-mail: a.krasnodembskaya@ 123456qub.ac.uk
          Author information
          http://orcid.org/0000-0002-2380-5069
          Article
          PMC5694830 PMC5694830 5694830 201701-0170OC
          10.1164/rccm.201701-0170OC
          5694830
          28598224
          9cdcfa80-9fab-4c95-b86a-9c751a22282e
          Copyright © 2017 by the American Thoracic Society
          History
          : 20 January 2017
          : 08 June 2017
          Page count
          Figures: 6, Tables: 2, Pages: 12
          Categories
          Original Articles
          Critical Care

          acute respiratory distress syndrome,extracellular vesicles,mesenchymal stromal cells,macrophages,mitochondria

          Comments

          Comment on this article