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.
Highlights
In the clinical application of tissue engineering (TE) products, it is crucial to prevent an immune rejection of the in vitro developed constructs
The difference in CD14 surface expression was not significant at day 7 compared to day 1. These results indicated that monocyte-derived dendritic cells (DCs) develop the typical expression profile after stimulation with both DC differentiation cocktails, providing a basis for the further co-cultivation experiments
The quantification of dendritic cell densities during DC maturation resulted in significant decreases when DCs were co-cultured with jaw periosteal cells (JPCs), whereby higher differences were observed in the tendency in co-cultures with undifferentiated JPCs, as shown in Figures 3–5
Summary
In the clinical application of tissue engineering (TE) products, it is crucial to prevent an immune rejection of the in vitro developed constructs. Biomaterials used for the generation of TE products, could induce an immune reaction. Efforts should be undertaken to develop biomaterials with low immunogenic potential. Some strategies involve the integration of immunosuppressive factors within the core material of biomaterials. These attempts fail, due to temporary but not persistent protection. The potential of mesenchymal stromal stem cells (MSCs) could help to create an immunosuppressive environment, avoiding an immune response
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