Abstract
BackgroundMesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3.MethodsWe conducted a prospective experimental interventional study on wild-type (WT) and PTX3-deficient (PTX3−/−) mice. Acute lung injury was induced in WT and PTX3−/− mice by instillation of hydrochloric acid into the right bronchus. One hour later, animals received intraperitoneal sterile phosphate-buffered saline (PBS), WT-MSCs (1 × 106) or PTX3−/−-MSCs (1 × 106). Twenty-four hours after injury, we measured the effects of treatments on arterial blood gases, wet/dry lung weight (W/D), CT scan analysis of lung collapse, neutrophils, TNFα and CXCL1 in bronchoalveolar lavage, and plasma PTX3. d-dimer was assayed in 1 week and OH-proline in 2 weeks to track the fibrotic evolution.ResultsIn 24 h, in comparison to PBS, WT-MSCs improved oxygenation and reduced W/D and alveolar collapse. These effects were associated with decreased concentrations of alveolar neutrophils and cytokines. WT-MSCs increased d-dimer concentration and decreased OH-proline levels, too.Treatment with PTX3−/−-MSCs ameliorated oxygenation, W/D, and alveolar TNFα, though to a lesser extent than WT-MSCs. PTX3−/−-MSCs did not improve lung collapse, neutrophil count, CXCL1, d-dimer, and OH-proline concentrations. The protective effects of WT-MSCs were dampened by lack of endogenous PTX3, too.ConclusionsIn acid aspiration acute lung injury, MSCs improve pulmonary function and limit fibrosis by fine-tuning inflammation. The role of PTX3 in determining MSCs’ effects might merit further scrutiny.
Highlights
Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury
Micro-CT scan analysis showed that the extent of lung collapse significantly decreased between 1 and 24 h in WT mice treated by wild-type MSCs (WT-MSCs) (p = 0.01), likely indicating decreased superimposed weight from reduced lung edema (Table 1 and Fig. 3), but not in those treated by phosphate-buffered saline (PBS)
Histology performed in 24 h showed decreased disruption of lung structures in mice treated by WT-MSCs in comparison to PBS (Table 1), even though this difference did not reach statistical significance
Summary
Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3. Overstimulation of leukocytes, cytokine storm, and altered tissue repair are key contributors to ARDS severity, mortality, and long-term morbidity [3]. The effects of i.p. MSCs have never been assessed in experimental acid aspiration acute lung injury [12]; the effects of MSCs on the fibrotic long-term evolution of acute lung injury [13] have not been described, and key molecular determinants of MSCs’ effects are not fully understood
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