Mesenchymal Stem Cells from Human Exfoliated Deciduous Teeth and the Orbicularis Oris Muscle: How Do They Behave When Exposed to a Proinflammatory Stimulus?

Abstract

Mesenchymal stem cells (MSCs) have been studied as a promising type of stem cell for use in cell therapies because of their ability to regulate the immune response. Although they are classically isolated from the bone marrow, many studies have sought to isolate MSCs from noninvasive sources. The objective of this study was to evaluate how MSCs isolated from the dental pulp of human exfoliated deciduous teeth (SHED) and fragments of the orbicularis oris muscle (OOMDSCs) behave when treated with an inflammatory IFN-γ stimulus, specifically regarding their proliferative, osteogenic, and immunomodulatory potentials. The results demonstrated that the proliferation of SHED and OOMDSCs was inhibited by the addition of IFN-γ to their culture medium and that treatment with IFN-γ at higher concentrations resulted in a greater inhibition of the proliferation of these cells than treatment with IFN-γ at lower concentrations. SHED and OOMDSCs maintained their osteogenic differentiation potential after stimulation with IFN-γ. Additionally, SHED and OOMDSCs have been shown to have low immunogenicity because they lack expression of HLA-DR and costimulatory molecules such as CD40, CD80, and CD86 before and after IFN-γ treatment. Last, SHED and OOMDSCs expressed the immunoregulatory molecule HLA-G, and the expression of this antigen increased after IFN-γ treatment. In particular, an increase in intracellular HLA-G expression was observed. The results obtained suggest that SHED and OOMDSCs lack immunogenicity and have immunomodulatory properties that are enhanced when they undergo inflammatory stimulation with IFN-γ, which opens new perspectives for the therapeutic use of these cells.

Easily attainable and low immunogenic stem cells from exfoliated deciduous teeth enhanced the in vivo bone regeneration ability of gelatin/bioactive glass microsphere composite scaffolds

“…MHC class II antigen HLA-DR binds to T-cell receptors during the immune response (Yang et al, 2021). SHED do not express HLA-DR even after stimulation with IFN-γ (Junior et al, 2020). With the properties of immunomodulatory functions, SHED is considered one of the most attractive cell sources for regenerative medicine (Sui et al, 2019).…”

“…In addition, SHED have a stronger proliferative capacity than BMMSs (Kunimatsu et al, 2018). Meanwhile, SHED have outstanding immunomodulatory and immunosuppressive potential (Junior et al, 2020), thus becoming promising candidates for transplantation.…”

In vitro evaluation of periapical lesion‐derived stem cells for dental pulp tissue engineering

“…Another crucial cytokine, HLA‐G, is a nonclassical MHC class I involved in immunomodulation by inhibiting the activation of natural killer cells and effector T cells [ 48 , 49 ]. A previous study reported that simulating the inflammatory environment of dental MSCs by incubating the cells with the pro‐inflammatory cytokine interferon‐γ results in increased HLA‐G expression in an interferon‐γ‐dependent manner [ 50 ]. Co‐culture experiments with peripheral blood mononuclear cells also drive the increased expression of IDO, soluble HLA‐G and HGF in MSCs [ 51 , 52 ].…”

Novel insights for improving the therapeutic safety and efficiency of mesenchymal stromal cells

“…, prostaglandin-endoperoxide synthase 2, prostaglandin I2 synthase, FAM20A (FAM20A golgi-associated secretory pathway pseudokinase), FAM20C (FAM20C golgi-associated secretory pathway kinase) and glycoprotein A repetitions predominant (GARP)/leucine rich repeat containing 32] that were upregulated. Moreover, MSCs isolated from the dental pulp of human exfoliated deciduous teeth and fragments of the orbicularis oris muscle showed enhanced immunomodulatory properties probably linked to increased HLA-G expression[ 48 ] in the presence of IFN-γ. Indeed, a recent study highlighted the key role of the HLA-G gene in modulating the immune response, and the importance of its polymorphisms and alleles associated with the outcome of the transplants[ 49 ].…”