{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:18:24Z","timestamp":1787811504196,"version":"build-2784847793"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012359","name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periodontal ligament (PDL) cells play a central role in periodontal tissue regeneration. We previously established induced pluripotent stem cell\u2013derived PDL-like cells (iPS-PDL) as a potential alternative cell source for regenerative therapy. However, the properties and biological functions of extracellular vesicles (EVs) released by iPS-PDL remain unknown. Characterizing these EVs may facilitate the development of cell-free approaches for periodontal regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to isolate and characterize EVs derived from iPS-PDL (iPS-PDL-EVs) and compare their biological functions with those of primary PDL cell\u2013derived EVs (PDL-EVs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EVs were isolated and purified using size exclusion chromatography and characterized by nanoparticle tracking analysis, scanning transmission electron microscopy, nano flow cytometry, and Western blotting. Their effects on PDL cell proliferation and migration were evaluated using WST-8 and Transwell assays. miRNA sequencing and bioinformatic analyses were performed to identify differentially expressed miRNAs and enriched biological pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      iPS-PDL-EVs and PDL-EVs exhibited typical EV characteristics. Compared with PDL-EVs, iPS-PDL-EVs significantly enhanced PDL cell proliferation and migration and activated MAPK and Akt signaling. Approximately 80% of the identified miRNAs were shared between the two EV populations; however, iPS-PDL-EVs contained elevated levels of miRNAs associated with MAPK signaling. miR-181a-2-3p suppressed\n                      <jats:italic>IL1R1<\/jats:italic>\n                      , whereas let-7i-5p and let-7g-5p suppressed\n                      <jats:italic>FAS<\/jats:italic>\n                      , thereby promoting PDL cell proliferation and migration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      iPS-PDL-EVs exhibit superior regenerative activity compared with PDL-EVs and may promote periodontal regeneration through miRNA-mediated signaling. These findings support the potential of iPS-PDL-EVs as a cell-free therapeutic strategy for periodontal regeneration. Future\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies are required to evaluate their therapeutic efficacy and safety.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1821829","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:35:10Z","timestamp":1787808910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles from induced pluripotent stem cell\u2013derived periodontal ligament cells enhance proliferation and migration of periodontal ligament cells for periodontal regeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Yurie","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Graduate School of Dentistry, Osaka Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Division of Creative and Integrated Medicine, Advanced Medicine Research Center, Translational Research Institute for Medical Innovation (TRIMI), Osaka Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomofumi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Biological Chemistry and Biologicals, National Institute of Health Sciences","place":["Kawasaki, Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ichiro","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Osaka Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"First Department of Oral and Maxillofacial Surgery, Osaka Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Momota","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Osaka, Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Biomaterials, Osaka Dental University","place":["Hirakata\/Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"950043","DOI":"10.3389\/fonc.2022.950043","article-title":"MiR-21 and let-7 cooperation in the regulation of lung cancer","volume":"12","author":"Bai","year":"2022","journal-title":"Front. 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