{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:59:54Z","timestamp":1783727994252,"version":"3.55.0"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19bK0104069h0002"],"award-info":[{"award-number":["JP19bK0104069h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regenerative Therapy"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.reth.2025.101059","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T04:35:48Z","timestamp":1768019748000},"page":"101059","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["First-in-human study to investigate the safety and efficacy of effective-mononuclear cell therapy for radiogenic xerostomia"],"prefix":"10.1016","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-5268","authenticated-orcid":false,"given":"Takashi","family":"I","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Iwatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hotokezaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Nishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Honma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munehiro","family":"Hayashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Nagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riho","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0639-1714","authenticated-orcid":false,"given":"Seigo","family":"Ohba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5766-1286","authenticated-orcid":false,"given":"Atsutoshi","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruchika","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Asahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Asahina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2999-1450","authenticated-orcid":false,"given":"Makoto","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Sumita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.reth.2025.101059_bib1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.oraloncology.2007.02.006","article-title":"A structured review and theme analysis of papers published on 'quality of life' in head and neck cancer: 2000-2005","volume":"43","author":"Rogers","year":"2007","journal-title":"Oral Oncol"},{"issue":"3","key":"10.1016\/j.reth.2025.101059_bib2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/154411130301400306","article-title":"Prevention and treatment of the consequences of head and neck radiotherapy","volume":"14","author":"Vissink","year":"2003","journal-title":"Crit Rev Oral Biol Med"},{"key":"10.1016\/j.reth.2025.101059_bib3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.oraloncology.2016.12.031","article-title":"Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: a systematic review and meta-analysis","volume":"66","author":"Mercadante","year":"2017","journal-title":"Oral Oncol"},{"issue":"4","key":"10.1016\/j.reth.2025.101059_bib4","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.ijrobp.2008.09.053","article-title":"Long-term outcomes and toxicity of concurrent paclitaxel and radiotherapy for locally advanced head-and-neck cancer","volume":"74","author":"Citrin","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"10.1016\/j.reth.2025.101059_bib5","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/odi.13294","article-title":"Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents","volume":"26","author":"Nicolatou-Galitis","year":"2020","journal-title":"Oral Dis"},{"key":"10.1016\/j.reth.2025.101059_bib6","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/1560175","article-title":"Role of periapical diseases in medication-related osteonecrosis of the jaws","volume":"2017","author":"Rao","year":"2017","journal-title":"BioMed Res Int"},{"issue":"8","key":"10.1016\/j.reth.2025.101059_bib7","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1002\/jbmr.379","article-title":"Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat","volume":"26","author":"Aghaloo","year":"2011","journal-title":"J Bone Miner Res"},{"issue":"4","key":"10.1016\/j.reth.2025.101059_bib8","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/odi.12708","article-title":"Risk factors for medication-related osteonecrosis of the jaws: a systematic review","volume":"24","author":"McGowan","year":"2018","journal-title":"Oral Dis"},{"issue":"8","key":"10.1016\/j.reth.2025.101059_bib9","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/j.joms.2020.12.045","article-title":"Factors influencing severity of medication-related osteonecrosis of the jaw: a retrospective study","volume":"79","author":"Feng","year":"2021","journal-title":"J Oral Maxillofac Surg"},{"issue":"2","key":"10.1016\/j.reth.2025.101059_bib10","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s00405-016-4367-9","article-title":"Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: adherence and exercise performance levels of a 12-week guided home-based program","volume":"274","author":"Cnossen","year":"2017","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"6","key":"10.1016\/j.reth.2025.101059_bib11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1056\/NEJM199308053290603","article-title":"Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer","volume":"329","author":"Johnson","year":"1993","journal-title":"N Engl J Med"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0360-3016(02)02890-0","article-title":"A Phase III placebo-controlled trial of oral pilocarpine in patients undergoing radiotherapy for head-and-neck cancer","volume":"54","author":"Warde","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"3","key":"10.1016\/j.reth.2025.101059_bib13","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.anl.2008.04.008","article-title":"Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese","volume":"36","author":"Nakamura","year":"2009","journal-title":"Auris Nasus Larynx"},{"issue":"8","key":"10.1016\/j.reth.2025.101059_bib14","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/j.joms.2020.12.045","article-title":"Factors influencing severity of medication-related osteonecrosis of the jaw: a retrospective study","volume":"79","author":"Feng","year":"2021","journal-title":"J Oral Maxillofac Surg"},{"key":"10.1016\/j.reth.2025.101059_bib15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0074-7696(02)13013-0","article-title":"Gene transfer to salivary glands","volume":"213","author":"Baum","year":"2002","journal-title":"Int Rev Cytol"},{"key":"10.1016\/j.reth.2025.101059_bib16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1111\/j.1600-0757.2006.00160.x","article-title":"Synergy between genetic and tissue engineering: creating an artificial salivary gland","volume":"41","author":"Baum","year":"2000","journal-title":"Periodontol"},{"issue":"5","key":"10.1016\/j.reth.2025.101059_bib17","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/odi.12320","article-title":"The potential use of cell-based therapies in the treatment of oral diseases","volume":"21","author":"Kagami","year":"2015","journal-title":"Oral Dis"},{"key":"10.1016\/j.reth.2025.101059_bib18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.semcdb.2013.12.001","article-title":"Salivary gland development: a template for regeneration","volume":"25\u201326","author":"Patel","year":"2014","journal-title":"Semin Cell Dev Biol"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.biocel.2010.10.010","article-title":"Bone marrow-derived cells: a potential approach for the treatment of xerostomia","volume":"43","author":"Tran","year":"2011","journal-title":"Int J Biochem Cell Biol"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib20","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1038\/s41467-018-06469-7","article-title":"Generation of orthotopically functional salivary gland from embryonic stem cells","volume":"9","author":"Tanaka","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.reth.2025.101059_bib21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-1-0716-1979-7_16","article-title":"Generation of salivary Gland organoids from mouse embryonic stem cells","volume":"2429","author":"Tanaka","year":"2022","journal-title":"Methods Mol Biol"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib22","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.biocel.2010.09.023","article-title":"Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation","volume":"43","author":"Sumita","year":"2011","journal-title":"Int J Biochem Cell Biol"},{"issue":"11","key":"10.1016\/j.reth.2025.101059_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0141862","article-title":"Adipose mesenchymal stem cell secretome modulated in hypoxia for remodeling of radiation-induced salivary gland damage","volume":"10","author":"An","year":"2015","journal-title":"PLoS One"},{"issue":"4","key":"10.1016\/j.reth.2025.101059_bib24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0061632","article-title":"Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation","volume":"8","author":"Tran","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib25","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s13287-019-1414-7","article-title":"Anti-inflammatory and vasculogenic conditioning of peripheral blood mononuclear cells reinforces their therapeutic potential for radiation-injured salivary glands","volume":"10","author":"I","year":"2019","journal-title":"Stem Cell Res Ther"},{"issue":"10","key":"10.1016\/j.reth.2025.101059_bib26","doi-asserted-by":"crossref","DOI":"10.3390\/cells12101417","article-title":"Immunomodulatory macrophages enable E-MNC therapy for radiation-induced salivary gland hypofunction","volume":"12","author":"Honma","year":"2023","journal-title":"Cells"},{"key":"10.1016\/j.reth.2025.101059_bib27","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.reth.2025.07.004","article-title":"Inhibition of the TLR4\/RAGE pathway by clearance of extracellular HMGB1 is a potential therapeutic target for radiation-damaged salivary glands","volume":"30","author":"I","year":"2025","journal-title":"Regen Ther"},{"key":"10.1016\/j.reth.2025.101059_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2023.1144624","article-title":"Effective-mononuclear cell (E-MNC) therapy alleviates salivary gland damage by suppressing lymphocyte infiltration in Sj\u00f6gren-like disease","volume":"11","author":"Hasegawa","year":"2023","journal-title":"Front Bioeng Biotechnol"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib29","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13063-017-1856-0","article-title":"First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial","volume":"18","author":"Gr\u00f8nh\u00f8j","year":"2017","journal-title":"Trials"},{"issue":"1","key":"10.1016\/j.reth.2025.101059_bib30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1186\/s13063-023-07594-5","volume":"24","author":"Jakobsen","year":"2023","journal-title":"Trials"}],"container-title":["Regenerative Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352320425002524?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352320425002524?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:00:16Z","timestamp":1773975616000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352320425002524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":30,"alternative-id":["S2352320425002524"],"URL":"https:\/\/doi.org\/10.1016\/j.reth.2025.101059","relation":{},"ISSN":["2352-3204"],"issn-type":[{"value":"2352-3204","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"First-in-human study to investigate the safety and efficacy of effective-mononuclear cell therapy for radiogenic xerostomia","name":"articletitle","label":"Article Title"},{"value":"Regenerative Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.reth.2025.101059","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine.","name":"copyright","label":"Copyright"}],"article-number":"101059"}}