Exploring the salivary proteome following intraglandular mesenchymal stromal cell therapy for radiation-induced hyposalivation in previous head and neck cancer patients: a secondary study protocol for the MESRIX-III, randomised, controlled trial.
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| Názov: | Exploring the salivary proteome following intraglandular mesenchymal stromal cell therapy for radiation-induced hyposalivation in previous head and neck cancer patients: a secondary study protocol for the MESRIX-III, randomised, controlled trial. |
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| Autori: | Carlander AF; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark. amanda-louise.fenger.carlander@regionh.dk., Jakobsen KK; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark., Jersie-Christensen R; Department of Science and Environment, Roskilde University, Roskilde, Denmark., Hansen J; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark., Bendtsen SK; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark., Kastrup J; Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen, Denmark., Belstrøm D; Department of Odontology, Section for Clinical Oral Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Lynggard CD; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark., Grønhøj C; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark., von Buchwald C; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark. |
| Zdroj: | Trials [Trials] 2025 Nov 28; Vol. 26 (1), pp. 554. Date of Electronic Publication: 2025 Nov 28. |
| Spôsob vydávania: | Journal Article; Clinical Trial Protocol |
| Jazyk: | English |
| Informácie o časopise: | Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2006- |
| Výrazy zo slovníka MeSH: | Xerostomia*/etiology , Xerostomia*/therapy , Xerostomia*/metabolism , Xerostomia*/diagnosis , Xerostomia*/physiopathology , Head and Neck Neoplasms*/radiotherapy , Mesenchymal Stem Cell Transplantation*/methods , Mesenchymal Stem Cell Transplantation*/adverse effects , Proteome*/metabolism , Saliva*/metabolism , Radiation Injuries*/etiology , Radiation Injuries*/metabolism , Radiation Injuries*/therapy , Radiation Injuries*/diagnosis , Radiation Injuries*/surgery , Salivary Proteins and Peptides*/metabolism, Humans ; Double-Blind Method ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Male ; Female ; Middle Aged ; Salivation ; Adult ; Time Factors |
| Abstrakt: | Competing Interests: Declarations. Competing interests: Lynggaard, Grønhøj and von Buchwald are co-inventors on patent application for “Stem cell therapy for patients with salivary gland dysfunction”, PCT/EP2020/053878, owned by Rigshospitalet, Copenhagen University Hospital and University of Copenhagen. Kastrup, Ekblond and Haack-Sørensen hold a patent application for the investigated stem cell product “Stem cell therapy based on adipose-derived stem cells”, WO2017068140 owned by Rigshospitalet, Copenhagen University Hospital and Capital Region of Denmark. All the other co-authors declare no conflicts of interest. Background: Intraglandular therapy with adipose-derived mesenchymal stromal cells (ASCs) for radiation-induced xerostomia and hyposalivation has shown promising effects on the salivary flow rate and in patient-reported outcomes. However, the mode of action is not fully understood, but changes in the salivary proteome have been observed. Methods: This sub study, to the randomised, double-blinded, placebo-controlled trial investigating intraglandular mesenchymal stromal cells for radiation-induced hyposalivation (MESRIX-III), examines changes in the salivary proteome following intraglandular therapy into the submandibular glands with allogenic ASCs in unstimulated whole saliva (UWS) in previous head and neck cancer patients with radiation-induced hyposalivation. A total of 120 patients were included and randomised in a 1:1 ratio to receive intraglandular injections with either ASCs or placebo (CryoStor10, 10% dimethyl sulfoxide, Biolife Solutions). UWS samples was collected at baseline and at 4 months post transplantation. The main endpoint is comparison of the salivary human proteome evaluated by mass spectrometry analysis in the group receiving ASCs compared to placebo at 4 months. Secondary outcomes are comparison of the microbial proteome in the group receiving ASCs compared to placebo at 4 months; changes in the salivary proteome and microbial proteome in the group receiving ASCs from baseline to 4 months and evaluation of the salivary proteome and microbial proteome following radiation therapy at baseline in both groups. Discussion: This study will gain insights into the potential mode of action of intraglandular ASC therapy for radiation-induced hyposalivation. The results may open avenues for a clinically applicable and disease-modifying treatment to ameliorate hyposalivation and restore salivary gland function following radiation therapy in previous head and neck cancer patients. Moreover, it will constitute the most extensive collection of data characterising the salivary proteome post-radiation therapy in the head and neck region. Trial Registration: The MESRIX-III study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee (protocol number: 1802872) and the Danish Medical Agency (2018-000348-24) and is registered at the ClinicalTrials.gov database (NCT04776538). First posted on clinicaltrials.gov 03-JAN-2021. (© 2025. The Author(s).) |
| References: | Clin Cancer Res. 2024 May 15;30(10):2078-2084. (PMID: 38441659) Crit Rev Oral Biol Med. 2003;14(3):199-212. (PMID: 12799323) CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338) Support Care Cancer. 2010 Aug;18(8):1039-60. (PMID: 20237805) Cochrane Database Syst Rev. 2017 Jul 31;7:CD012744. (PMID: 28759701) Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 Mar;117(3):335-342.e1. (PMID: 24528792) Stem Cell Rev Rep. 2024 May;20(4):1078-1092. (PMID: 38430363) Commun Med (Lond). 2022 Dec 10;2(1):160. (PMID: 36496530) Radiother Oncol. 2015 Jul;116(1):45-50. (PMID: 26002304) Stem Cells Transl Med. 2022 May 27;11(5):478-489. (PMID: 35435231) Trials. 2023 Sep 1;24(1):567. (PMID: 37658468) J Clin Oncol. 2008 Aug 1;26(22):3770-6. (PMID: 18669465) Bioinformatics. 2014 Jul 15;30(14):2068-9. (PMID: 24642063) Ther Clin Risk Manag. 2015 Feb 04;11:171-88. (PMID: 25691810) Int J Radiat Oncol Biol Phys. 2018 Jul 1;101(3):581-592. (PMID: 29678523) J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53):. (PMID: 31425600) Clin Cancer Res. 2022 Jul 1;28(13):2890-2897. (PMID: 35486613) Crit Rev Oral Biol Med. 2003;14(3):213-25. (PMID: 12799324) Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):751-60. (PMID: 17560735) Ann Intern Med. 2013 Feb 5;158(3):200-7. (PMID: 23295957) |
| Grant Information: | 2020-352-14024-1 Candys Foundation |
| Contributed Indexing: | Keywords: Hyposalivation; MSC; Mesenchymal stem/stromal cells; Mesenchymal stromal cells; Proteome; Proteomics; Radiation therapy; Xerostomia |
| Molecular Sequence: | ClinicalTrials.gov NCT04776538 |
| Substance Nomenclature: | 0 (Proteome) 0 (Salivary Proteins and Peptides) |
| Entry Date(s): | Date Created: 20251129 Date Completed: 20251129 Latest Revision: 20251201 |
| Update Code: | 20251201 |
| PubMed Central ID: | PMC12664238 |
| DOI: | 10.1186/s13063-025-09074-4 |
| PMID: | 41316394 |
| Databáza: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: Declarations. Competing interests: Lynggaard, Grønhøj and von Buchwald are co-inventors on patent application for “Stem cell therapy for patients with salivary gland dysfunction”, PCT/EP2020/053878, owned by Rigshospitalet, Copenhagen University Hospital and University of Copenhagen. Kastrup, Ekblond and Haack-Sørensen hold a patent application for the investigated stem cell product “Stem cell therapy based on adipose-derived stem cells”, WO2017068140 owned by Rigshospitalet, Copenhagen University Hospital and Capital Region of Denmark. All the other co-authors declare no conflicts of interest.<br />Background: Intraglandular therapy with adipose-derived mesenchymal stromal cells (ASCs) for radiation-induced xerostomia and hyposalivation has shown promising effects on the salivary flow rate and in patient-reported outcomes. However, the mode of action is not fully understood, but changes in the salivary proteome have been observed.<br />Methods: This sub study, to the randomised, double-blinded, placebo-controlled trial investigating intraglandular mesenchymal stromal cells for radiation-induced hyposalivation (MESRIX-III), examines changes in the salivary proteome following intraglandular therapy into the submandibular glands with allogenic ASCs in unstimulated whole saliva (UWS) in previous head and neck cancer patients with radiation-induced hyposalivation. A total of 120 patients were included and randomised in a 1:1 ratio to receive intraglandular injections with either ASCs or placebo (CryoStor10, 10% dimethyl sulfoxide, Biolife Solutions). UWS samples was collected at baseline and at 4 months post transplantation. The main endpoint is comparison of the salivary human proteome evaluated by mass spectrometry analysis in the group receiving ASCs compared to placebo at 4 months. Secondary outcomes are comparison of the microbial proteome in the group receiving ASCs compared to placebo at 4 months; changes in the salivary proteome and microbial proteome in the group receiving ASCs from baseline to 4 months and evaluation of the salivary proteome and microbial proteome following radiation therapy at baseline in both groups.<br />Discussion: This study will gain insights into the potential mode of action of intraglandular ASC therapy for radiation-induced hyposalivation. The results may open avenues for a clinically applicable and disease-modifying treatment to ameliorate hyposalivation and restore salivary gland function following radiation therapy in previous head and neck cancer patients. Moreover, it will constitute the most extensive collection of data characterising the salivary proteome post-radiation therapy in the head and neck region.<br />Trial Registration: The MESRIX-III study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee (protocol number: 1802872) and the Danish Medical Agency (2018-000348-24) and is registered at the ClinicalTrials.gov database (NCT04776538). First posted on clinicaltrials.gov 03-JAN-2021.<br /> (© 2025. The Author(s).) |
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| ISSN: | 1745-6215 |
| DOI: | 10.1186/s13063-025-09074-4 |