Mechanisms and clinical application potential of mesenchymal stem cells-derived extracellular vesicles in periodontal regeneration

Abstract Periodontitis is a high prevalence oral disease which damages both the hard and soft tissue of the periodontium, resulting in tooth mobility and even loss. Existing clinical treatment methods cannot fully achieve periodontal tissue regeneration; thus, due to the unique characteristics of mesenchymal stem cells (MSCs), they have become the focus of attention and may be the most promising new therapy for periodontitis. Accumulating evidence supports the view that the role of MSCs in regenerative medicine is mainly achieved by the paracrine pathway rather than direct proliferation and differentiation at the injured site. Various cells release lipid-enclosed particles known as extracellular vesicles (EVs), which are rich in bioactive substances. In periodontitis, EVs play a pivotal role in regulating the biological functions of both periodontal tissue cells and immune cells, as well as the local microenvironment, thereby promoting periodontal injury repair and tissue regeneration. As a cell-free therapy, MSCs-derived extracellular vesicles (MSC-EVs) have some preponderance on stability, immune rejection, ethical supervision, and other problems; therefore, they may have a broad clinical application prospect. Herein, we gave a brief introduction to MSC-EVs and focused on their mechanisms and clinical application in periodontal regeneration.