Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis

Amanda Louise Fenger Carlander*, Anders Kierkegaard Gundestrup, Per Marcus Jansson, Bjarke Follin, Cecilie Hoeeg, Birgitte Saima Kousholt, Rasmus Tolstrup Larsen, Kathrine Kronberg Jakobsen, Susie Rimborg, Anne Fischer-Nielsen, Christian Grønhøj, Christian von Buchwald, Charlotte Duch Lynggaard

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

Background: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. Methods: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO (www.crd.ac.uk/prospero), registration number CRD42021227336. Results: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55–11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. Conclusion: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting. Graphical Abstract: (Figure presented.)

Original languageEnglish
JournalStem Cell Reviews and Reports
Volume20
Issue4
Pages (from-to)1078-1092
Number of pages15
ISSN2629-3269
DOIs
Publication statusPublished - May 2024

Keywords

  • Cell Therapy
  • Mesenchymal stem Cells
  • Radiotherapy
  • Systematic Review
  • Xerostomia

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