Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents

Abstract

BackgroundAdult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties.MethodsGMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE).ResultsTNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions.ConclusionsA high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0880-7) contains supplementary material, which is available to authorized users.

Phytochemical Profile, Antioxidant and Antidiabetic Activities of Adansonia digitata L. (Baobab) from Mali, as a Source of Health-Promoting Compounds

“…The volume of the injected extract solutions was 20 μL. All analyses were performed with an ESI interface in the negative mode in a scan range of m / z 150–2000 and the ionization conditions were optimized as follows: capillary temperature, 270 °C; source voltage, 4.50 kV; capillary voltage, −16.0 V; tube lens offset, −5.0 V; sheath gas flow rate, 60.00 arbitrary units; auxiliary gas flow rate, 3.00 arbitrary units; spray voltage, 4.50 kV [37]. N 2 was used as the sheath and auxiliary gas.…”

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

“…Among these, a pivotal role is played by IL-6 and TGF-β as inducers of GMT and cancer growth, IL-10 as a modulator of immune response and the chemoattractant IL-8 as a promoter of GBM motility [ 53 ]. The ability of BM-MSCs to release these cytokines in response to extracellular stimuli has been reported previously [ 54 ]. To investigate the effects of ADO on BM-MSC secretome composition, the BM-MSCs were treated with two ADO concentrations and the levels of secreted cytokines were analyzed ( Figure 4 C).…”

“…Interestingly, ADO regulates the induction of GMT in U343MG almost in part through the increase of ERK1/2 phosphorylation. The EMT process is tightly controlled, and several intracellular mechanisms are involved in its regulation including ERK1/2 phosphorylation [ 54 ]. The ability of ADO to increase ERK 1/2 phosphorylation in airway epithelia cells has been reported previously [ 85 ].…”

“…Recently, Iser et al [ 57 ] demonstrated that the CM derived by adipose-derived MSCs promote the EMT process in C6 cells. These effects are supported by the ability of MSCs to secrete soluble factors such as IL-6 and TGF-β [ 54 ], which are two key players in the promotion of a transition to a mesenchymal phenotype [ 93 ]. Our results support the capacity of BM-MSC to release soluble factors able to promote the expression of the transcription factors such as Snail and Twist.…”

Novel positive allosteric modulators of A2B adenosine receptor acting as bone mineralisation promoters

“…Treatments were repeated every 3 days and the mineralisation was quantified after 15 days of treatment. The rate of mineralisation was quantified using alizarin red staining as previously reported 32 . Briefly, cells were washed with PBS, fixed (4% formaldehyde in PBS) for 15 min and washed three times with PBS.…”