THU0041 MESENCHYMAL STEM CELLS OF DIFFERENT ORIGINS EXHIBIT UNIQUE RESPONSES TO DIFFERENT INFLAMMATORY STIMULI

Background: Mesenchymal stromal/stem cell (MSC) - based therapies represent promising avenues for treatment of various inflammatory and autoimmune diseases. Currently, a variety of fetal and adult tissues represent a good source of MSC, however further characterization of their effects, especially in an inflammatory environment, is needed. Objectives: Firstly, to characterize MSC from different origins, namely bone marrow (BM), adipose tissue (AT) and umbilical cord (UC), after stimulation with TNFα, IL-1β and serum amyloid A (SAA). Secondly, to determine the effects of MSC secretome on migration, proliferation and apoptosis of lung fibroblasts. Methods: BM-, AT- or UC-MSC were isolated each from 3 healthy donors. The expression and secretion of analytes were studied in each cell type at basal level and followingTNFα- (1 ng/ml), IL-1β- (1 ng/ml) and SAA- (12 µg/ml) stimulation using qPCR (SDF, CCL5, VCAM, PDE, PGC, IDO, VEGF, IGF) and Luminex technology (IL-6, IL8, MCP-1, ICAM, CH3L1, MMP1, MMP3, tenascin, uPA, HGF, VEGF), respectively. Normal healthy lung fibroblasts (NHLF) were used in the wound scratch assay and treated for 24h with 20% of MSC-conditioned media. For evaluation of BM-, AT- and UC conditioned media effects on proliferative and apoptotic activity, Ki-67-immunolabeled mitotic cells and caspase-3-immunolabeled cells were counted using fluorescence microscopy. Results: Treatment of MSC with pro-inflammatory cytokines increased mRNA levels of SDF, CCL5, VCAM1, PGC and IDO, while levels of PDE-5A were down-regulated. The greatest increase in expression was observed in TNFα-stimulated MSCs, namely of two immunomodulatory molecules, CCL5 and IDO in AT-MSC (4396- and 928-fold change increase respectively). Secretome analysis showed highest secretion levels of IL-6, IL-8 and MCP1 after IL-1β-activation in all 3 tissue sources. AT- and BM-derived conditioned media increased NHLF scratch closure, while UC-MSC decreased it. In non-inflammatory conditions, UC-, BM- and AT- MSCs conditioned media decreased the number of mitotic events in NHLF by an average of 40%. Importantly, only the conditioned medium derived from inflammatory cytokine-treated AT- and BM-MSC significantly decreased the mitotic rate of NHLF (p Conclusion: Our results highlight specific roles of MSC from different tissue origins, as well as their response to environmental inflammatory stimuli and suggest that source selection might be critical for the success of treatment approaches in different diagnoses. Disclosure of Interests: None declared