{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:21:58Z","timestamp":1785770518680,"version":"3.56.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013826","name":"Candys Foundation","doi-asserted-by":"publisher","award":["2017-218"],"award-info":[{"award-number":["2017-218"]}],"id":[{"id":"10.13039\/501100013826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001275","name":"Oak Foundation","doi-asserted-by":"publisher","award":["OCAY-18-774-OFIL"],"award-info":[{"award-number":["OCAY-18-774-OFIL"]}],"id":[{"id":"10.13039\/100001275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)\u2014xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem\/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&amp;N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL\/minute at baseline to 0.18 mL\/minute with a change of 0.06 (P = .0009) mL\/minute. SWS flow rate increased from 0.66 mL\/minute at baseline to 0.75 mL\/minute with a change of 0.09 (P = .017) mL\/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&amp;N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 (P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.<\/jats:p>","DOI":"10.1093\/stcltm\/szac011","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T20:12:01Z","timestamp":1646424721000},"page":"478-489","source":"Crossref","is-referenced-by-count":39,"title":["Intraglandular Off-the-Shelf Allogeneic Mesenchymal Stem Cell Treatment in Patients with Radiation-Induced Xerostomia: A Safety Study (MESRIX-II)"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-2146","authenticated-orcid":false,"given":"Charlotte Duch","family":"Lynggaard","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark"},{"name":"Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gr\u00f8nh\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Christensen","sequence":"additional","affiliation":[{"name":"Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital , Copenhagen , Denmark"},{"name":"Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital , Odense , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fischer-Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Melchiors","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-2190","authenticated-orcid":false,"given":"Lena","family":"Specht","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark"},{"name":"Department of Oncology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Herlev Hospital, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-8995","authenticated-orcid":false,"given":"Jann","family":"Mortensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark"},{"name":"Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Oturai","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gry Hoffmann","family":"Barfod","sequence":"additional","affiliation":[{"name":"AGiR, Department of Geoscience, Aarhus University , Aarhus C , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Kannik","family":"Haastrup","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00f8ller-Hansen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandana","family":"Haack-S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Ekblond","sequence":"additional","affiliation":[{"name":"Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen 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