A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

Abstract

Recent advances in mesenchymal stem/stromal cell (MSC) research have led us to consider the feasibility of MSC-based therapy for various diseases. Human dental pulp-derived MSCs (hDPSCs) have been identified in the dental pulp tissue of deciduous and permanent teeth, and they exhibit properties with self-renewal and in vitro multipotency. Interestingly, hDPSCs exhibit superior immunosuppressive functions toward immune cells, especially T lymphocytes, both in vitro and in vivo. Recently, hDPSCs have been shown to have potent immunomodulatory functions in treating systemic lupus erythematosus (SLE) in the SLE MRL/lpr mouse model. However, the mechanisms underlying the immunosuppressive efficacy of hDPSCs remain unknown. This review aims to introduce a new target of hDPSC-based therapy on the recipient niche function in SLE.

Keywords: cell-cell interaction; cellular microenvironment; dental pulp; immunomodulation; mesenchymal stem cells; systemic lupus erythematosus.

Figure 1

Class and characterization of human dental pulp-derived stem cells (hDPSCs). hDPSCs can be isolated from dental pulp tissues of deciduous, permanent, supernumerary teeth, and apical papillae of immature tooth roots, such as impacted wisdom teeth. hDPSCs exhibit mesenchymal stem cell (MSC)-like phenotypes and functions, including the adherent colony-forming capacity of colony-forming unit-fibroblasts (CFU-F), MSC marker expression, multipotent differentiation into osteoblasts, adipocytes, and chondrocytes, and immunosuppressive function. DPSCs, dental pulp stem cells; SCAP, stem cells from apical papilla; SHED, stem cells from exfoliated human deciduous teeth; SNTSCs, human supernumerary tooth-derived stem cells; Mø, macrophages.

Figure 2

Immunosuppressive mechanism of hDPSC transplantation in systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemically administrated donor hDPSCs release extracellular vesicles, hDPSC-derived Evs (hDPSC-Evs), and are incorporated into recipient bone marrow MSCs of MRL/lpr mice (lpr-BMMSCs). The RNA contained within the hDPSC-Evs are transferred into the lpr-BMMSCs to epigenetically enhance telomerase reverse transcriptase gene (Tert) expression, improving the SLE disorders of MRL/lpr mice via recipient BMMSC-mediated niche reconstruction and immunosuppressive function. Th17, interleukin 17 helper T lymphocytes; Treg, regulatory T lymphocytes.