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Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are potential candidates for improving human health. In this work, we studied the effect of Ptychotis verticillata (PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML. [ABSTRACT FROM AUTHOR]

Background: As a cell-based therapeutic, AT-MSCs need to create an immuno-reparative environment appropriate for tissue repair. In the presence of injury, MSCs may have to proliferate and face inflammation. Clinical application requires repeated administrations of a high number of cells with a well-established immune profile. Methods: We have established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was performed during cell-expansion and inflammatory priming of AT-MSCs. Results: Our study confirms that AT-MSCs are highly expandable and sensitive to inflammation. Both conditions have substantially modulated the expression of a panel of immunological marker. Specifically, CD34 expression was substantially decreased upon cell-passaging. HLA-ABC, CD40 CD54, CD106, CD274 and CD112 were significantly increased by inflammation. In vitro cell-expansion also significantly altered the expression profile of HLA-DR, CD40, CD62L, CD106, CD166, HLA-G, CD200, HO-1, CD155 and ULBP-3. Conclusion: This study points out the response and characteristics of MSCs following expansion and inflammatory priming. It will strength our knowledge about the molecular mechanisms that may improve or hamper the therapeutic potential of MSCs. These immunological changes need to be further characterized to guarantee a safe cellular product with consistent quality and high therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Stem cells have been the focus of intense research opening up new possibilities for the treatment of various diseases. Mesenchymal stromal cells (MSCs) are multipotent cells with relevant immunomodulatory properties and are thus considered as a promising new strategy for immune disease management. To enhance their efficiency, several issues related to both MSC biology and functions are needed to be identified and, most importantly, well clarified. The sources from which MSCs are isolated are diverse and might affect their properties. Both clinicians and scientists need to handle a phenotypic-characterized population of MSCs, particularly regarding their immunological profile. Moreover, it is now recognized that the tissue-reparative effects of MSCs are based on their immunomodulatory functions that are activated following a priming/licensing step. Thus, finding the best ways to pre-conditionate MSCs before their injection will strengthen their activity potential. Finally, soluble elements derived from MSC-secretome, including extracellular vesicles (EVs), have been proposed as a cell-free alternative tool for therapeutic medicine. Collectively, these features have to be considered and developed to ensure the efficiency and safety of MSC-based therapy. By participating to this Special Issue "Mesenchymal Stem/Stromal Cells in Immunity and Disease", your valuable contribution will certainly enrich the content and discussion related to the thematic of MSCs. [ABSTRACT FROM AUTHOR]