Table 1 Postulated mechanisms of action of stem cells in pre-clinical models of ALI/ARDS

Mesenchymal stem cells

Ortiz et al. 2007 [41]

Murine bleomycin

IV

Secretion of IL-1 receptor antagonist

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

Xu et al. 2007 [55]

Murine IP LPS

IV 1 hour post-injury

Production of soluble factors by MSCs that promote an anti-inflammatory cytokine milieu

Paracrine effect was enhanced by cell to cell contact

Production of chemoattractants for MSCs by lung cells

Gupta et al. 2007 [40]

Murine IT LPS

IT 4 hours post-LPS

Paracrine effect by MSCs in downregulating the inflammatory response

Engraftment rate <5%

Lee et al. 2009 [33]

Ex vivo perfused human lung

IT 1 hour post-LPS

Secretion of KGF by MSCs resulting in improved endothelial permeability and restoration of alveolar epithelium fluid transport

Németh et al. 2009 [44]

Murine CLP

IV 24 hours pre-injury

Prostaglandin E2-dependent reprogramming of macrophage to increase production of IL-10

Mei et al. 2010 [28]

Murine CLP

IV 6 hours post-injury

Modification of inflammatory gene transcriptional activity

Down-regulation of the acute inflammatory response and up-regulation of pathways relevant to phagocytosis and bacterial clearance

Krasnodembskaya et al. 2010 [29]

E. coli pneumonia

IT 4 hours post-injury

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

Danchuk et al. 2011 [46]

Murine LPS

IV, OA and IP human MSCs

Secretion of TSG-6 by MSCs resulting in reduced neutrophil recruitment and activation

Secretion of KGF

Endothelial progenitor cells

Lam et al. 2008 [76]

Rabbit oleic acid

IV 30 minutes post-injury

Reduced expression of iNOS

Reduced lung leukocyte count

Decreased pulmonary oedema, lung haemorrhage and hyaline membrane formation

Mao et al. 2010 [56]

Rat LPS

IV 30 minutes post-injury

Anti-inflammatory-increased IL-10

Decreased pulmonary oedema, lung haemorrhage

Reduced iNOS and ET-1 expression

Embryonic stem cells

Wang et al. 2010 [88]

Murine bleomycin

IT 1 or 2 days post-injury

Improved oxygenation

Decreased collagen deposition

Increased survival

Foetal stem cells

Moodley et al. 2009 [94]

Murine bleomycin

IV 24 hours post-injury

Anti-inflammatory-reduced IL-1, IL-6, MCP-1

Anti-fibrotic-reduced TGF-β