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Table 1 Therapeutics role of MSCs in the pre-clinical models of ALI/ARDS

From: Therapeutic implications of mesenchymal stem cells in acute lung injury/acute respiratory distress syndrome

MSC delivery route

Lung injury model

Mechanism of therapy

Reference

IV delivery immediately post-injury

Murine IT bleomycin-induced ALI

Engrafted male cells were localized to areas of bleomycin-induced injury and exhibited an epithelium-like morphology

[28]

Reduced the degree of bleomycin-induced inflammation and collagen deposition within lung tissue

IV delivery 6 h post-injury

Murine IT bleomycin-induced ALI

Differentiation of engrafted BMDMSC into specific and distinct lung cell phenotypes

[29]

An increase in circulating levels of G-CSF and GM-CSF and with a decrease in inflammatory cytokines

IT delivery 4 h and 24 h post-injury

Murine IT LPS-induced ALI

Significant decrease in excess lung water, pulmonary edema, bronchoalveolar lavage protein, endothelial and alveolar epithelial permeability

[35]

IT delivery 1 h and 24 h post-injury

Endotoxin-induced ALI in ex vivo perfused human lung

Secretion of KGF by mesenchymal stem cells resulting in improved endothelial permeability and restoration of alveolar epithelium fluid transport

[36]

IV delivery immediately post-injury

Murine IT bleomycin-induced ALI

Secretion of IL-1 receptor antagonist

[37]

Inhibition of TNF-α production by macrophage and IL-1a-dependent T cell line

IV delivery 1 h and 24 h post-injury

Murine IP LPS-induced ALI

Prevented endotoxin-induced lung inflammation, injury, and edema

[39]

Suppressed the endotoxin-induced increase in circulating pro-inflammatory cytokines without decreasing circulating levels of anti-inflammatory mediators

IV delivery immediately post-injury

Murine IT bleomycin-induced ALI

Promoted Th1 phenotype and inhibited Th2-mediated allergic airways inflammation

[44]

IT delivery 4 h post-injury

Murine IT LPS-induced ALI

Diminished levels of alveolar CD4 + CD25 + Foxp3 + Treg and balancing anti- and pro-inflammatory factors

[46]

IV delivery 6 h and 24 h post-injury

Murine CLP-induced ALI

Modification of inflammatory gene transcriptional activity

[48]

Downregulation of the acute inflammatory response and upregulation of pathways relevant to phagocytosis and bacterial clearance

IT delivery 4 h and 24 h post-injury

E. coli pneumonia-induced ALI

Secretion of the anti-microbial peptide LL-37 resulting in increased bacterial clearance

[49]

  1. ALI, acute lung injury; ARDS, acute respiratory distress syndrome; BMDMSC, bone marrow-derived mesenchymal stem cell; CLP, cecal ligation and puncture; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IP, intraperitoneal; IT, intratracheal; IV, intravenous; KGF, keratinocyte growth factor; LPS, lipopolysaccharide; MSC, mesenchymal stem cell.