Earlier studies have documented ben

Earlier studies have documented beneficial effects of MSCs derived from bone marrow or umbilical cord tissue in bacterial pneumonia models [18, 21, 23, 51–54]. Most studies used Escherichia (E.) coli to infect mice or rats via the airways, reporting reduced pulmonary edema and alveolar epithelial permeability, attenuated proinflammatory cytokine release, and enhanced bacterial clearance after i.v. or intratracheal administration of MSCs [18, 23, 51–53]. The E. coli model relates more to acute lung injury than pneumonia and strongly differs from the K. pneumoniae model used here: whereas the E. coli model is associated with acute onset severe lung inflammation and clearance of bacteria, our model is associated with a steadily growing bacterial load and a gradually evolving inflammatory response eventually resulting in sepsis, thereby better resembling the clinical scenario of bacterial pneumonia. Intratracheal administration of bone marrow derived MSCs reduced alveolitis and protein leakage in experimental pneumonia induced by a K. pneumoniae strain different from the one used here, while not influencing bacterial loads [21]. We here evaluated the therapeutic potential of MSCs derived from adipose tissue, which more recently has become an attractive source of MSCs due to its higher content of stem cells [27] and because ASCs may be acquired through procedures less invasive than bone marrow aspiration [28, 29]. One previous study addressed the effects of ASCs (derived from mouse adipose tissue) in bacterial pneumonia: in experimental respiratory tract infection caused by Pseudomonas aeruginosa, which like the E. coli model was associated with acute lung injury and clearance of bacteria from the airways. Intratracheal administration of ASCs reduced bacterial burden, protein leak, the extent of lung injury, inhibited chemokine release, and neutrophil influx [24]. ASCs have also been reported to exert antiinflammatory effects in models of noninfectious acute lung injury [55]. The present data are in line with and extend on these previous studies, suggesting that both freshly cultured and cryopreserved ASCs administered via a clinically relevant route (i.v.) influence host defense in a model of bacterial pneumonia that resembles human infection