TY - JOUR T1 - Characterization of human mesenchymal stem cells phenotype and secretome in a in vitro model of acute lung injury inflammation JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4589 AU - Arnaud Goolaerts AU - Valérie Vanneaux AU - Jérôme Larghero AU - Michael Matthay AU - Christine Clérici Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4589.abstract N2 - Intra-tracheal instillation of MSCs have therapeutic efficacy in models of acute lung injury (ALI). Protective effects of MSC are reported despite low engraftment rates supporting that paracrine mediators may be involved. In ALI, MSCs delivered by intra-tracheal route are exposed to alveolar hypoxia and cytokines, both known to independently modify MSC phenotype, which may affect their survival or their reparative properties. We therefore investigated the effects of a typical alveolar ALI microenvironment consisting in hypoxia (HYP) and cytomix (CYT; IL-1β, TNFα and INFγ) on MSC phenotype, apoptosis and secretion profile. Testing the effects of such conditions is important to better understand the fate and behavior of MSC instilled into injured lungs and to detect potential modification of their secretion profile. In order to decide whether MSC preconditioning might be an interesting strategy, MSC were exposed 24 hours to CYT 50ng/ml and/or HYP (0% O2). CYT and/or HYP neither modify the expression of the typical MSCs markers (CD90, CD105, CD45) nor the degree of apoptosis/necrosis when compared to control MSCs. We measured KGF, PGE2 and IL-1 receptor antagonist (IL-1rA) in the supernatant because they are known to be important for resolution of alveolar edema. Compared to control conditions, CYT plus HYP increased the release of PGE2 (190±160 vs 2999±261 ng/ml), IL1-rA (0 vs 134±26 ng/ml) but decreased by two fold the release of KGF (345±8 vs 115±12,8 ng/ml). In conclusion: Hypoxic and inflammatory environment mimicking ALI does not affect the survival and phenotype of MSC but differentially modulates KGF, PGE-2 and IL-1rA secretion. ER -