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Updated: Jun 24, 2025

Establishing Organoids from Human Tooth as a Powerful Tool Toward Mechanistic Research and Regenerative Therapy
Published on: April 13, 2022
Odontogenesis-Empowered Extracellular Vesicles Safeguard Donor-Recipient Stem Cell Interplay to Support Tooth
Xiaoyao Huang1,2, Bingdong Sui1, Anqi Liu2,3
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Disease, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Stem cells from human exfoliated deciduous teeth (SHED) aggregates promote tooth regeneration by restoring periodontal tissues and activating recipient stem cells via extracellular vesicles (EVs). These EVs are key to communication and regeneration, enabling cell-free therapeutic strategies.
Area of Science:
- Dental stem cell biology
- Regenerative medicine
- Extracellular vesicle research
Background:
- Tooth avulsion is a common dental injury requiring effective regeneration strategies.
- Stem cells from human exfoliated deciduous teeth (SHED) aggregates show promise in clinical trials for avulsed tooth revitalization.
- The communication mechanisms between SHED aggregates and recipient tissues for synergistic regeneration are not fully understood.
Purpose of the Study:
- To elucidate the mechanisms by which SHED aggregates (SA) promote avulsed tooth regeneration.
- To investigate the role of stem cell communication in supporting replanted teeth.
- To explore the potential of cell-free strategies using extracellular vesicles (EVs) for tooth regeneration.
Main Methods:
- Utilized stem cells from human exfoliated deciduous teeth (SHED) to form aggregates (SA).
- Investigated the interaction of SA with recipient tissues, focusing on Gli1+ stem cells and periodontal restoration.
- Analyzed the role of extracellular vesicles (EVs) released from SA (SA-EVs) in mediating stem cell mobilization and regeneration.
- Assessed the therapeutic potential of SA-EVs in avulsed tooth regeneration models.
Main Results:
- SA-mediated regeneration involves periodontal restoration and the mobilization of recipient Gli1+ stem cells.
- Extracellular vesicles (EVs) released from SA are essential for mobilizing recipient stem cells and regenerating avulsed teeth.
- SHED aggregates-released EVs (SA-EVs) possess odontogenic properties, enhancing Gli1+ cell migration, proliferation, and differentiation.
- Local application of SA-EVs alone effectively promotes regeneration of avulsed teeth by empowering recipient Gli1+ cells.
Conclusions:
- SHED aggregates orchestrate avulsed tooth regeneration through intercellular communication mediated by EVs.
- Odontogenesis-associated EVs play a crucial role in governing donor-recipient stem cell interactions for tooth regeneration.
- These findings support the development of cell-free therapeutic strategies using EVs for regenerative dentistry.
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