{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:21:37Z","timestamp":1772983297883,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270964"],"award-info":[{"award-number":["82270964"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470964"],"award-info":[{"award-number":["82470964"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Dental pulp stem cells (DPSCs) regulate immune responses; however, their heterogeneity in deep caries remains unclear. This study aimed at investigating the role of intercellular adhesion molecule 1\u2010positive DPSCs (ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs) within the immune microenvironment of deep carious pulp tissue to develop therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Single\u2010cell sequencing was used to compare cellular profiles between deep caries and healthy pulp tissues. ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs were quantified using immunofluorescence\/flow cytometry in human\/mouse models and sorted for functional analyses. Odontogenic differentiation was assessed using alkaline phosphatase\/Alizarin Red staining, while inflammatory mediator production was assessed using RT\u2010qPCR, Western Blot, ELISA, SCENIC and RNA\u2010seq. THP\u20101 was cultured in conditioned media from ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs and ICAM1\n                      <jats:sup>\u2212<\/jats:sup>\n                      DPSCs. RT\u2010qPCR, Western Blot and flow cytometry were used to assess the proportion of proinflammatory to reparative THP\u20101. Macrophage\u2010derived cytokines (IL\u20101\u03b2\/4\/6\/10 and TNF\u2010\u03b1) were tested for DPSCs to ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      differentiation induction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cellular profiling showed a significant increase in ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs and proinflammatory monocytes in deep carious dental pulp tissue, with ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs closely interacting with mononuclear macrophages. Immunofluorescence and flow cytometry confirmed the increase in ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs in deep caries in the affected human and mouse pulp tissue. Alkaline phosphatase and Alizarin Red staining, SCENIC, RT\u2010qPCR, Western Blot and ELISA revealed decreased odontogenic differentiation in ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs and increased expression of CEBPD, IL\u20106, CCL2 and CXCL10 in ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSC cells. RT\u2010qPCR, Western Blot and flow cytometry indicated an elevated proinflammatory to reparative THP\u20101 ratio for THP\u20101 that was cultured in ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSC\u2010conditioned media for 1\u20133\u2009days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      During deep caries progression, TNF\u2010\u03b1 drives the transformation of DPSCs into inflammatory ICAM1\n                      <jats:sup>+<\/jats:sup>\n                      DPSCs. This subcluster exhibits impaired odontogenic differentiation capacity, secretes proinflammatory cytokines and chemokines, and enhances macrophage inflammatory activity, contributing to the advancement of deep caries lesions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.14248","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:16:05Z","timestamp":1748337365000},"page":"1184-1196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of intercellular adhesion molecule 1\u2010positive dental pulp stem cells in deep caries progression"],"prefix":"10.1111","volume":"58","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiatong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research 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