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Here, we successfully regenerated tooth pulp in the root canal of minipigs by transplanting human deciduous tooth stem cells (SHED). The implanted SHED differentiated into several functional cells, particularly Schwann cells (SCs), which attracted and enwrapped regrown host axons in regenerated pulp. The reciprocal extracellular vesicles (EVs) communication between SHED and the host trigeminal ganglion (TG) regulated the regeneration of dental nerves. EVs derived from SHED (SHED\u2010EVs) facilitated axonal growth, while those released by TG neurons (TGN) induced the differentiation of SHED into SCs. TGN that engulfed SHED\u2010EVs secreted endogenous EVs (ST\u2010EVs) and migrated to the regenerated pulp tissue. ST\u2010EVs from TGN are enriched with TUFM (Tu translation elongation factor, mitochondrial), which, in turn promotes Schwann cell differentiation (SC differentiation) of SHED. This study highlights the importance of cellular signal exchange during the integration of donor cells and host tissues for organ regeneration.<\/jats:p>","DOI":"10.1002\/exp2.70229","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:59:21Z","timestamp":1791518361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endogenous Trigeminal Neurons Induce Schwann Differentiation of Donor Stem Cells in Dental Pulp Regeneration via Reciprocal Extracellular Vesicles Interplay"],"prefix":"10.1002","author":[{"given":"Wanmin","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"},{"name":"Department of Stomatology Air Force Medical Center The Fourth Military Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Endodontics School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dihao","family":"Tao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"},{"name":"Department of Stomatology Air Force Medical Center The Fourth Military Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghan","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Growth Metabolism and Aging Key Laboratory of Bio\u2010Resource and Eco\u2010Environment of Ministry of Education College of Life Sciences Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center For Oral Diseases Center For Tissue Engineering School of Stomatology The Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Shi","sequence":"additional","affiliation":[{"name":"South China Center of Craniofacial Stem Cell Research Guanghua School of Stomatology Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and K.K. 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