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Due to the constraints of autologous and allogeneic transplantation, stem cell-based regenerative therapies present a promising alternative. As a crucial source of cell therapy, mesenchymal stem cells (MSCs) are widely employed for tissue regeneration on account of their exceptional proliferative capacity and multidirectional differentiation potential. Nevertheless, several challenges remain in clinical application, such as the immunogenicity, long-term safety, and therapeutic efficacy. This review centers on the application of craniomaxillofacial MSCs in the treatment of craniomaxillofacial congenital defects and the challenges confronted in regenerative therapy, aiming to provide new perspectives for the clinical management of these conditions.<\/jats:p>","DOI":"10.3390\/biom15070953","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Craniomaxillofacial-Derived MSCs in Congenital Defect Reconstruction"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaona","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuan","family":"Bian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/bdr2.1345","article-title":"The role of 3D printing in treating craniomaxillofacial congenital anomalies","volume":"110","author":"Lopez","year":"2018","journal-title":"Birth Defects Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s12015-010-9197-3","article-title":"Human stem cell cultures from cleft lip\/palate patients show enrichment of transcripts involved in extracellular matrix modeling by comparison to controls","volume":"7","author":"Bueno","year":"2011","journal-title":"Stem Cell Rev. 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