Interactions between human 2D- and 3D-cultured jaw periosteal and dendritic cells

Abstract

This thesis investigated the immunoregulatory properties of 2D-cultured human periosteal cells as well as their effects in the 3D culture within β-TCP constructs on monocyte-derived DC maturation. Furthermore, the impact of extracellular Zn ion concentrations on periosteal cell response was evaluated. Based on the experimental results, the principal findings can be summarized as follows: 1) After co-culturing with 2D-cultured JPCs, DC numbers were significantly decreased. At the same time, gene expressions of IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were decreased while IL-8 mRNA levels were increased. These data showed that 2D-cultured JPCs elicit an overall immunosuppressive effect on monocyte-derived DC maturation. 2) After co-culturing with JPCs-seeded β-TCP scaffolds, lower dendritic cell densities and mature/immature DC ratios were detected, probably due to its overall inhibition of pro-inflammatory (IFN-γ) and induction of the anti-inflammatory cytokines (IL-10 and G-CSF). This study demonstrated an overall inhibitory effect of JPCs-seeded β-TCP constructs on monocyte-derived DC maturation. 3) The third study revealed that low extracellular Zn ion concentrations can significantly induce the osteogenesis of immortalized periosteal cells while the high Zn ion concentration seemed to inhibit its osteogenic differentiation, implying a dose-dependent effect of this element. To sum up, JPCs exhibit excellent characteristics and can be considered as a promising stem cell source for bone tissue engineering. Further, appropriate Zn ion concentrations effectively improved osteogenic differentiation of immortalized periosteal cells. To continue this research topic, future investigations should focus the interactions of JPCs with other members of the innate immune system, e.g. macrophages and the analysis of the underlaying mechanism in more details. As a further aspect, the influence of Zn ions on primary periosteal cells should be elucidated.