Effects of Jaw Periosteal Cells on Dendritic Cell Maturation

Abstract

Clinical application of tissue engineering products requires the exclusion of immune responses after implantation. We used jaw periosteal cells (JPCs) as a suitable stem cell source and analyzed herein the effects of JPCs on dendritic cell maturation after co-culturing of both cell types. Peripheral blood mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the addition of differentiation cocktails for 7 days in co-culture with undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC maturation were analyzed at the beginning (day 7), in the middle (day 14), and at the end (day 21) of the osteogenesis process. We detected significantly lower DC numbers after co-culturing with JPCs that have previously been left untreated or osteogenically differentiated for 7, 14, and 21 days. Using gene expression analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were detected, whereas IL-8 mRNA levels were significantly higher in DCs. Furthermore, osteogenic media conditions enhanced significantly IL-10 gene expression. We concluded that undifferentiated and osteogenically differentiated JPCs had an overall inhibiting influence on dendritic cell maturation. Further studies should clarify the underlaying mechanism in depth.

Jaw Periosteal Cells Seeded in Beta-Tricalcium Phosphate Inhibit Dendritic Cell Maturation

“…Human bone marrow-derived MSCs possess the ability to inhibit human monocytic-derived DC differentiation [37]. In our previous study, we could demonstrate that undifferentiated and osteogenically differentiated two-dimensionally cultivated JPCs are potentially capable of suppressing DC maturation in the coculture [30]. In the present study, three-dimensionally cultured JPCs within β-TCP scaffolds significantly decreased DC numbers during DC maturation, as shown in Figures 1 and 2A.…”

“…Human bone marrow-derived MSCs possess the ability to inhibit human monocytic-derived DC differentiation [ 37 ]. In our previous study, we could demonstrate that undifferentiated and osteogenically differentiated two-dimensionally cultivated JPCs are potentially capable of suppressing DC maturation in the coculture [ 30 ]. In the present study, three-dimensionally cultured JPCs within β-TCP scaffolds significantly decreased DC numbers during DC maturation, as shown in Figure 1 and Figure 2 A. Additionally, Figure 2 B shows that the ratio of suspension cells (corresponding to mature DCs) to adherent cells (corresponding to immature DCs) was significantly lower when DCs were cocultured with JPCs-seeded β-TCP constructs compared to that of monocultures of the respective media.…”

“…Numerous studies have proven that MSCs not only can inhibit DC maturation [26,27] but also can inhibit T cells proliferation [28,29] due to their low immunogenicity and immunoregulatory properties. Previously, we reported that JPCs exhibit an overall inhibiting effect on DC maturation in a 2D Transwell system [30].…”

“…Samples from three donors were included in the study, with the approval number 194/2008BO2 from the local ethics committee. After obtaining written informed consent from these three donors, human JPCs were isolated and cultured, as mentioned previously [18,30]. JPCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F-12, Invitrogen/Thermo Fisher Scientific, Waltham, USA) containing 10% fetal calf serum (FCS) (Sigma-Aldrich, Darmstadt, Germany), 1% penicillin/streptomycin (Lonza, Basel, Switzerland), and 1% fungicides (Biochrom AG, Berlin, Germany) under standard cell culture conditions.…”

“…Pooled JPCs of these three donors from the sixth passage were used for all coculture experiments, and cell culture medium was replaced every other day. The osteogenic differentiation potential of the used JPCs was evaluated as reported before [30].…”