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Background: AT-MSCs display great immunoregulatory features, making them potential candidates for cell-based therapy. This study aimed to evaluate the "RBC lysis buffer" isolation protocol and immunological profiling of the so-obtained AT-MSCs., Methods: We established an immune-comparative screening of AT-MSCs throughout in vitro cell expansion (PM, P1, P2, P3, P4) and inflammatory priming regarding the expression of 28 cell-surface markers, 6 cytokines/chemokines, and 10 TLR patterns., Findings: AT-MSCs were highly expandable and sensitive to microenvironment challenges, hereby showing plasticity in distinct expression profiles. Both cell expansion and inflammation differentially modulated the expression profile of CD34, HLA-DR, CD40, CD62L, CD200 and CD155, CD252, CD54, CD58, CD106, CD274 and CD112. Inflammation resulted in a significant increase in the expression of the cytokines IL-6 , IL-8 , IL-1β , IL-1Ra , CCL5 , and TNFα . Depending on the culture conditions, the expression of the TLR pattern was distinctively altered with TLR1-4 , TLR7 , and TLR10 being increased, whereas TLR6 was downregulated. Protein network and functional enrichment analysis showed that several trophic and immune responses are likely linked to these immunological changes., Conclusions: AT-MSCs may sense and actively respond to tissue challenges by modulating distinct and specific pathways to create an appropriate immuno-reparative environment. These mechanisms need to be further characterized to identify and assess a molecular target that can enhance or impede the therapeutic ability of AT-MSCs, which therefore will help improve the quality, safety, and efficacy of the therapeutic strategy.

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.

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (© 2019 Wiley Periodicals, Inc.)

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.

Objective and Design: Bone marrow mesenchymal stromal cells (BM-MSCs) are referred as a promising immunotherapeutic cell product. New approaches using empowered MSCs should be developed as for the treatment or prevention of different immunological diseases. Such preconditioning by new licensing stimuli will empower the immune fate of BM-MSCs and, therefore, promote a better and more efficient biological. Here, our main goal was to establish the immunological profile of BM-MSCs following inflammatory priming and in particular their capacity to adjust their immune-related proteome and transcriptome., Material and Methods: To run this study, we have used BM-MSC cell cultures, a pro-inflammatory cytokine cocktail priming, flow cytometry analysis, qPCR and ELISA techniques., Results: Different expression levels of several immunological mediators such as COX-1, COX-2, LIF, HGF, Gal-1, HO-1, IL-11, IL-8, IL-6 and TGF-β were constitutively observed in BM-MSCs. Inflammation priming substantially but differentially modulated the gene and protein expression profiles of these mediators. Thus, expressions of COX-2, LIF, HGF, IL-11, IL-8 and IL-6 were highly increased/induced and those of COX-1, Gal-1, and TGF-β were reduced., Conclusions: Collectively, we demonstrated that BM-MSCs are endowed with a specific and modular regulatory machinery which is potentially involved in immunomodulation. Moreover, BM-MSCs are highly sensitive to inflammation and respond to such signal by properly adjusting their gene and protein expression of regulatory factors. Using such preconditioning may empower the immune fate of MSCs and, therefore, enhance their value for cell-based immunotherapy.

Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation potential and potent immunomodulatory capacity, represent a promising, safe and powerful cell based-therapy for repairing tissue damage and/or treating diseases associated with aberrant immune responses. Natural killer (NK) cells are granular lymphocytes of the innate immune system that function alone or in combination with other immune cells to combat both tumors and virally infected cells. After their infusion, MSCs are guided by host inflammatory elements and can interact with different immune cells, particularly those of the innate immune system. Although some breakthroughs have been achieved in understanding these interactions, much remains to be determined. In this review, we discuss the complex interactions between NK cells and MSCs, particularly the importance of improving the therapeutic value of MSCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Mesenchymal stromal cells (MSCs) are multipotent adult cells with relevant biological properties making them interesting tools for cell-based therapy. These cells have the ability to home to sites of injury and secrete bioactive factors as part of their therapeutic functions. However, depending on the local environment, diverse functions of MSCs can be modulated and thus can influence their therapeutic value. The specific cytokine milieu within the site of inflammation is vital in determining the fate and cell behaviors of MSCs. Indeed, inflammatory signals (called as inflammatory priming), may induce critical changes on the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects. In summary, investigating MSC interactions with the inflammatory environment is necessary to empower the therapeutic value of MSCs.

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., (© 2017 International Federation for Cell Biology.)

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]