Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

Oral stem cells,decoding and mapping the resident cells populations

The teeth and their supporting tissues provide an easily accessible source of oral stem cells.These different stem cell populations have been extensively studied for their properties,such as high plasticity and clonogenicity,expressing stem cell markers and potency for multilineage differentiation in vitro.Such cells with stem cell properties have been derived and characterised from the dental pulp tissue,the apical papilla region of roots in development,as well as the supporting tissue of periodontal ligament that anchors the tooth within the alveolar socket and the soft gingival tissue.Studying the dental pulp stem cell populations in a continuously growing mouse incisor model,as a traceable in vivo model,enables the researchers to study the properties,origin and behaviour of mesenchymal stem cells.On the other side,the oral mucosa with its remarkable scarless wound healing phenotype,offers a model to study a well-coordinated system of healing because of coordinated actions between epithelial,mesenchymal and immune cells populations.Although described as homogeneous cell populations following their in vitro expansion,the increasing application of approaches that allow tracing of individual cells over time,along with single-cell RNA-sequencing,reveal that different oral stem cells are indeed diverse populations and there is a highly organised map of cell populations according to their location in resident tissues,elucidating diverse stem cell niches within the oral tissues.This review covers the current knowledge of diverse oral stem cells,focusing on the new approaches in studying these cells.These approaches“decode”and“map”the resident cells populations of diverse oral tissues and contribute to a better understanding of the“stem cells niche architecture and interactions.Considering the high accessibility and simplicity in obtaining these diverse stem cells,the new findings offer potential in development of translational tissue engineering approaches and innovative therapeutic solutions.