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.
Cell Differentiation ; Extracellular Vesicles/metabolism* ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stem Cells/metabolism*

Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.
Wound Healing/physiology* ; Mesenchymal Stem Cells ; Extracellular Vesicles ; Stem Cell Transplantation

Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.
Humans ; Extracellular Vesicles ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mesenchymal Stem Cell Transplantation/methods* ; Mesenchymal Stem Cells ; Pharmaceutical Preparations

Mesenchymal stem cells (MSC) have been widely used in tissue regeneration and treatment graft versus host disease (GVHD) and immune diseases due to their self-renewal, multi-differentiation and immunoregulatory potential. However, more and more scholars begin to put weight on the MSC -derived extracellular vesicles (MSC-EV) for its regulation of inflammation and immunity. MSC-EV can activate the relevant signal pathways and regulate the function and biological behaviors of cells via acting on target cells and mediating communication between cells. MSC-EV has important potential clinical applications for its powerful immunomodulatory and hematopoietic regulatory functions. It is considered as a potential therapeutic tool to treat autoimmune diseases and GVHD. This paper reviewed the immunomodulatory activity of MSC-EV as well as the research progress of MSC-EV in hematopoietic stem cell transplantation, and discussed its potential clinical applications in the future.
Cell Differentiation ; Extracellular Vesicles/transplantation* ; Graft vs Host Disease/metabolism* ; Hematopoietic Stem Cell Transplantation ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells