Dental stem cell-derived extracellular vesicles as promising therapeutic agents in the treatment of diseases

Abstract

Dental stem cells (DSCs), an important source of mesenchymal stem cells (MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles (DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the (I) distinguishing features of DSC-EVs compared with other types of MSC-EVs, (II) heterogeneity among different subtypes of DSC-derived EVs, (III) action modes of DSC-EVs, (IV) standardization for eligible DSC-EVs and (V) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.

Extracellular vesicles delivering nuclear factor I/C for hard tissue engineering: Treatment of apical periodontitis and dentin regeneration

“… 32 – 34 Recently, EVs have gained more attention as a protection or repair mechanism against pulp infection, and it was found that EV derived from LPS-stimulating dental cells protect cells from apoptosis and promote the proliferation, migration, and differentiation of several dental stem cells, 12 – 15 however, our data here found that EV derived from LPS-stimulated DPCs suppressed odontoblastic differentiation of SCAPs, which suggests a pathological role of EV in AP progression. The paradoxical roles of LPS-stimulated EV can be attributed to the heterogeneity among different subtypes of dental cells-derived EVs, 35 meanwhile, given the variation of LPS concentration and precondition time duration between each study, another explanation is that a different role of LPS-stimulated EVs may be associated with the severity of infection.…”

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication

“…Similarly, the transfer of RNA through EVs secreted by SC-like differentiated adipose stem cells has been shown to promote neurite outgrowth ( Ching et al, 2018 ). The proliferation and maintenance of human dental pulp cells have also been shown to be promoted by SDEVs ( Li et al, 2022 ).…”

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis

“…Therefore, DPSC-sEV may be acquired more conveniently with higher production and bioactivities than BMSC-sEV. DPSC-sEV have also been documented to exert therapeutic effects on skin wounds, spinal cord injury, and mandible and calvarial bone defects [ 18 , [21] , [22] , [23] , [24] ]. However, it is largely unknown whether DPSC-sEV can simultaneously directly suppress the macrophage inflammatory response and osteoclastogenesis to induce bone repair in inflammatory osteolysis.…”