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As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs. [ABSTRACT FROM AUTHOR]

The emerging role of MSCs in creating a protective and immune-tolerant microenvironment may support the survival of tumor cells and affect the response to therapies. Importantly, the pre-conditioning or engineering of MSCs may strengthen the anti-cancer immune response by generating pro-inflammatory MSCs or EVs with anti-tumor effects in parallel, to increase the cytotoxic functions of immune effector cells. The conflicting roles of MSCs in tumor inhibition and tumor growth impede their adaptation for anticancer therapies. [Extracted from the article]

Objective and design: Mesenchymal stromal cells (MSCs) are currently used in cell reparative medicine due to their trophic and ant-inflammatory properties. The modulation of stem cell properties by phytochemicals has been suggested as a tool to empower their tissue repair capacity. In vitro, MSCs are characterized by their tri-lineage potential that holds great interest for tissue regeneration. Ptychotis Verticillata (PV), an aromatic and medicinal plant, may be thus used to modulate the in vitro multilineage potential of MSCs. Materials and methods: We screened the impact of PV-derived essential oil and their bioactive molecules (thymol and carvacrol) on the in vitro multilineage potential of MSCs. Different concentrations and incubation times of these compounds were assessed during the osteogenesis and adipogenesis of MSCs. Results: The analysis of 75 conditions indicates that these compounds are biologically active by promoting two major differentiation lineages from MSCs. In a time- and dose-dependent manner, thymol and carvacrol increased the osteogenesis and adipogenesis. Conclusion: According to these preliminary observations, the addition of PV extract may stimulate the tissue regenerative and repair functions of MSCs. Further optimization of compound extraction and characterization from PV as well as cell treatment conditions should increase their therapeutic value in combination with MSCs. [ABSTRACT FROM AUTHOR]

Adipose tissue‐derived mesenchymal stromal cells (ASCs) hold the promise of achieving successful immunotherapeutic results due to their ability to regulate different T‐cell fate. ASCs also show significant adaptability to environmental stresses by modulating their immunologic profile. Cell‐based therapy for inflammatory diseases requires a detailed understanding of the molecular relation between ASCs and Th17 lymphocytes taking into account the influence of inflammation and cell ratio on such interaction. Accordingly, a dose‐dependent increase in Th17 generation was only observed in high MSC:T‐cell ratio with no significant impact of inflammatory priming. IL‐23 receptor (IL‐23R) expression by T cells was not modulated by ASCs when compared to levels in activated T cells, while ROR‐γt expression was significantly increased reaching a maximum in high (1:5) unprimed ASC:T‐cell ratio. Finally, multiplex immunoassay showed substantial changes in the secretory profile of 15 cytokines involved in the Th17 immune response (IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17A, IL‐17F, IL‐22, IL‐21, IL‐23, IL‐25, IL‐31, IL‐33, IFN‐γ, sCD40, and TNF‐α), which was modulated by both cell ratio and inflammatory priming. These findings suggest that Th17 lymphocyte pathway is significantly modulated by ASCs that may lead to immunological changes. Therefore, future ASC‐based immunotherapy should take into account the complex and detailed molecular interactions that depend on several factors including inflammatory priming and cell ratio. [ABSTRACT FROM AUTHOR]

Objective and design: The objective of the study is to uncover the influence of human bone marrow-derived mesenchymal stem cells (BM-MSCs) on the generation of Th17 lymphocytes in co-cultures of both BM-MSCs and T cells.Materials and methods: BM-MSCs, characterized according to the international society for cellular therapy (ISCT) criteria, were co-cultured with T cells isolated from peripheral blood. The expression levels of IL-17 receptor, RORγt and IL-23 receptor were evaluated using flow cytometry. The levels of cytokines involved in Th17 immunomodulation were measured using multiplex assay.Treatment: Inflammatory primed and non-primed BM-MSCs were co-cultured with either activated or non-activated T cells either at (1/80) and (1/5) ratio respectively.Results: MSC/T-cell ratio and inflammation significantly influenced the effect of BM-MSCs on the generation of Th17 lymphocytes. Cocultures of either primed or non-primed BM-MSCs with activated T cells significantly induced IL-17A-expressing lymphocytes. Interestingly, the expression of the transcription factor RORγt was significantly increased when compared to levels in activated T cells. Finally, both cell ratio and priming of BM-MSCs with cytokines substantially influenced the cytokine profile of BM-MSCs and T cells.Conclusion: Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stromal cells (MSCs) display a special immunological profile that allows their potential use as immunotherapeutic cells. Nowadays, foreskin (FSK) represents a valuable reservoir of MSCs with International Society for Cellular Therapy (ISCT) compliant criteria and relevant functional properties. However, their mode of action is poorly understood and needs to be more elucidated to optimize their therapeutic use. Because microRNAs (miRNAs) act as key regulators in a wide variety of biological processes, we decided to establish the micronome of FSK‐MSCs, the influence of inflammation and the predicted target pathways. Here, we provide the full list of unchanged and additional four differentially expressed miRNAs, miR‐199b, ‐296‐3p and ‐589‐5p being downregulated whilst miR‐146‐3p being upregulated, in MSCs following their exposure to a cocktail of proinflammatory cytokines. MicroRNA target prediction in addition to Pathway enrichment analysis performed using miRNet, showed that miR‐296‐3p is linked to antigen processing and presentation pathway. Collectively, our data indicate that the micronome of FSK‐MSCs is partially responsive to inflammation. Differentially expressed miRNAs are subsequently modulated by inflammation and seem to be involved in regulating the immunological fate of FSK‐MSCs. These miRNAs deserve more attention in order to optimize MSC‐based therapy and achieve the appropriate therapeutic effect. [ABSTRACT FROM AUTHOR]

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]

Mesenchymal stem/stromal cells (MSCs) are considered a relevant therapeutic product for various clinical applications. MSCs are not immune cells but tissue precursor cells with immunomodulatory features that show important interplay and interactions with other tissue progenitor cells. Though largely debated, the presence of circulating endogenous MSCs (native MSCs) has been reported in multiple pathophysiological conditions, but the significance of such cell circulation is not known and therapeutically untapped [[2]]. [Extracted from the article]

In this Special Issue, directed and supervised by Dr. Mehdi Najar, a collection of basic research articles and reviews, on the state of the art of Mesenchymal Stem/Stromal Cells (MSCs) immune biology, is presented. Among the major goals of this Special Issue is the presentation of an update about the immunomodulatory properties of MSCs and their capacity to respond to tissue microenvironment changes. MSCs hold great promise in the field of immunotherapy and regenerative medicine. Accordingly, a better understanding of MSC immune biology will improve their therapeutic value and use. [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]

Mesenchymal stromal cells (MSCs) represent a progenitor cell population with several biological properties. MSCs are thus of therapeutic interest for cell-based therapy but great efforts are needed to enhance their efficiency and safety. Herbal remedies and in particular their bioactive molecules, are potential candidates for improving human health. The novelty and originality of this study is to develop an efficient cell-therapeutic product by combining MSCs with medicinal plant derived bioactive molecules. Thus, the impact of Essential Oil, Thymol and Carvacrol from Ptychotis verticillata on several BM-MSC biological features were studied. These compounds have shown positive effects on MSCs by preserving their morphology, sustaining their viability, promoting their proliferation, protecting them from cytotoxicity and oxidative stress. Accordingly, the combined administration of P. verticillata extract and MSCs may represent a new approach to enhance the therapeutic issue. Further investigations should greatly improve the manufacturing of these compounds as well as our understanding of the therapeutic effects of these bioactive molecules on the biology and functions of MSCs. • Mesenchymal stromal cells (MSCs) are major therapeutic cell progenitors which efficiency needs to be improved. • Ptychotis verticillata derived bioactive molecules are tested as potential candidates for improving MSC efficacy. • MSC morphology, viability, proliferation and oxidative response are differentially influenced. • Combined administration of P. verticillata extract and MSCs may represent a new therapeutic approach. • Amelioration of compound manufacturing and characterization will increase their therapeutic value in combination with MSCs. [ABSTRACT FROM AUTHOR]