Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists

Abstract

Yanyi Wang,1,2,* Juan Wen,1– 3,* Tong Lu,1,2 Wei Han,2,4 Kai Jiao,5 Huang Li1,2 1Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia; 4Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 5Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Han, Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Email [email protected] Huang Li, Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.Keywords: extracellular vesicles, mesenchymal stem cells, functional modification, bone-related diseases

Keywords

• extracellular vesicles
• mesenchymal stem cells
• functional modification
• bone-related diseases