Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration

Abstract

Mesenchymal stem cells (MSCs) are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory ability. Dental tissue-derived MSCs can be isolated from different sources, such as the dental pulp, periodontal ligament, deciduous teeth, apical papilla, dental follicles and gingiva. According to numerous in vitro studies, the effect of dental MSCs on immune cells might depend on several factors, such as the experimental setting, MSC tissue source and type of immune cell preparation. Most studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune cells. MSCs exert mostly immunosuppressive effects, leading to the dampening of immune cell activation. Thus, the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease progression. Although the immunomodulatory potential of dental MSCs has been extensively investigated in vitro, its role in vivo remains obscure. A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ability. Moreover, the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease severity. MSC-based immunomodulation may play an essential role in the regeneration of different dental tissues. Therefore, immunomodulation-based strategies may be a very promising tool in regenerative dentistry.

Keywords: Dental tissue; Immunomodulation; Mesenchymal stem cells; Oral diseases; Peripheral blood mononuclear cells; Tissue regeneration.

Figure 1

Reciprocal interaction between dental tissue-derived mesenchymal stem cells and immune cells. While the immunomodulatory ability of resting mesenchymal stem cells (MSCs) is usually low, inflammatory cytokines such as interferon-γ, tumour necrosis factor-α, and interleukin-1β lead to strong activation of this ability. Large amounts of these cytokines are produced by immune cells, such as peripheral blood mononuclear cells (PBMCs) or macrophages, under inflammatory conditions. In vitro cytokine production can be activated by either mitotic stimuli or bacterial pathogens. Inflammatory cytokines increase the expression of different immunomodulatory proteins in MSCs, which leads to the suppression of the activity of PBMCs or directs macrophage polarization towards the M2 phenotype via paracrine mechanisms or direct cell-to-cell contact. The resulting lower levels of the inflammatory cytokines produced by PBMCs or macrophages diminish the ability of these cells to activate MSC-dependent immunosuppression. Thus, the continuous interaction between immune cells and dental tissue-derived MSCs determines the intensity of the immune response and hypothetically plays an important role in tissue homeostasis.