Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis

Per Marcus Jansson, Charlotte Duch Lynggaard*, Amanda Fenger Carlander, Siri Beier Jensen, Bjarke Follin, Cecilie Hoeeg, Birgitte Saima Kousholt, Rasmus Tolstrup Larsen, Christian Grønhøj, Kathrine Kronberg Jakobsen, Susie Rimborg, Anne Fischer-Nielsen, Julia M L Menon, Christian von Buchwald

*Corresponding author for this work
2 Citations (Scopus)


BACKGROUND: Salivary gland (SG) hypofunction (objectively reduced saliva flow rate) and xerostomia (subjective sensation of dry mouth) are common and burdensome side effects of radiotherapy to the head and neck region. Currently, only sparse symptomatic treatment is available to ease the discomfort of xerostomia. The objective of this study is to assess the effect of mesenchymal stem cell (MSC) therapy on SG function after radiation-induced injury.

METHODS: This systematic review will include animal intervention studies assessing efficacy and safety of MSCs in treating radiation-induced SG hypofunction. The primary outcome is the effect of MSC administration on salivary flow rates (SFR), by comparing treated groups to control groups when available. Secondary outcomes are morphological and immunohistochemical effects as well as safety of MSC treatment. Electronic searches in MEDLINE (PubMed) and Embase databases will be constructed and validated according to the peer review of electronic search strategies (PRESS) and assessed by two independent researchers. Data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Risk of bias will be evaluated with the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool.

DISCUSSION: Thus far, critical appraisal of MSC therapy as an effective treatment for SG hypofunction caused solely by radiation injury has not been conducted. A summary of the existing literature on preclinical studies concerning this issue can provide valuable information about effectiveness, mode of action, and safety, allowing further optimization of preclinical and clinical trials.


Original languageEnglish
Article number72
JournalSystematic Reviews
Issue number1
Publication statusPublished - 18 Apr 2022


  • Animals
  • Humans
  • Mesenchymal Stem Cells
  • Meta-Analysis as Topic
  • Salivary Glands
  • Stem Cell Transplantation
  • Systematic Reviews as Topic
  • Xerostomia/etiology
  • Systematic review
  • Radiotherapy
  • Xerostomia
  • Stem cells
  • Salivary gland hypofunction


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