Stem cell conditioned medium improves acute lung injury in mice

In vivo evidence for stem cell paracrine action

Lavinia Ionescu, Roisin N. Byrne, Tim van Haaften, Arul Vadivel, Rajesh S. Alphonse, Gloria J. Rey-Parra, Gaia Weissmann, Adam Hall, Farah Eaton, Bernard Thébaud

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donorderived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSCand fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/antiinflammatory M2 macrophage phenotype in part via IGF-I.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume303
Issue number11
DOIs
Publication statusPublished - 2012

Fingerprint

Acute Lung Injury
Conditioned Culture Medium
Mesenchymal Stromal Cells
Stem Cells
Lung Injury
Lipopolysaccharides
Lung
Insulin-Like Growth Factor I
Fibroblasts
Phenotype
Arginase
Macrophage Activation
Adult Respiratory Distress Syndrome
Alveolar Macrophages
Therapeutic Uses
Nitric Oxide Synthase Type II
Wound Healing

Keywords

  • Cell therapy
  • Lung injury
  • Repair

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Stem cell conditioned medium improves acute lung injury in mice : In vivo evidence for stem cell paracrine action. / Ionescu, Lavinia; Byrne, Roisin N.; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S.; Rey-Parra, Gloria J.; Weissmann, Gaia; Hall, Adam; Eaton, Farah; Thébaud, Bernard.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 303, No. 11, 2012.

Research output: Contribution to journalArticle

Ionescu, L, Byrne, RN, van Haaften, T, Vadivel, A, Alphonse, RS, Rey-Parra, GJ, Weissmann, G, Hall, A, Eaton, F & Thébaud, B 2012, 'Stem cell conditioned medium improves acute lung injury in mice: In vivo evidence for stem cell paracrine action', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 303, no. 11. https://doi.org/10.1152/ajplung.00144.2011
Ionescu, Lavinia ; Byrne, Roisin N. ; van Haaften, Tim ; Vadivel, Arul ; Alphonse, Rajesh S. ; Rey-Parra, Gloria J. ; Weissmann, Gaia ; Hall, Adam ; Eaton, Farah ; Thébaud, Bernard. / Stem cell conditioned medium improves acute lung injury in mice : In vivo evidence for stem cell paracrine action. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2012 ; Vol. 303, No. 11.
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