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The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions are closely related to pathogen invasion and an overreactive immune response. It is worth noting that the protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) have a crucial function in mediating the immune system and promoting regeneration. Here, we review the recent studies related to AP, with a focus on the regulatory network of MSCs. We also discuss the potential therapeutic approaches of MSCs in inflammatory diseases to provide a basis for promoting tissue regeneration and modulating inflammation in AP. A deeper understanding of the protective action of MSCs and the regulatory networks will help to delineate the underlying mechanisms of AP and pave the way for stem-cell-based regenerative medicine in the future.<\/jats:p>","DOI":"10.3390\/biom12121737","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"1737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Ping","family":"Lyu","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Song","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiye","family":"Bi","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zucen","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Wei","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-7343","authenticated-orcid":false,"given":"Chen","family":"Cui","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Stomatology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzhe","family":"Song","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Fan","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/iej.13467","article-title":"The global prevalence of apical periodontitis: A systematic review and meta-analysis","volume":"54","author":"Michelon","year":"2021","journal-title":"Int. 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