Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients

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  • Charlotte Duch Lynggaard, University of Copenhagen
  • ,
  • Rosa Jersie-Christensen, Department of Haematology, Roskilde University Hospital, Roskilde, Denmark.
  • ,
  • Morten Juhl, University of Copenhagen
  • ,
  • Siri Beier Jensen
  • Christian Grønhøj, University of Copenhagen
  • ,
  • Jacob Melchiors, University of Copenhagen
  • ,
  • Søren Jacobsen, University of Copenhagen
  • ,
  • Michael Møller-Hansen, University of Copenhagen
  • ,
  • Mikkel Herly, University of Copenhagen
  • ,
  • Annette Ekblond, University of Copenhagen
  • ,
  • Jens Kastrup, University of Copenhagen
  • ,
  • Anne Fischer-Nielsen, University of Copenhagen
  • ,
  • Daniel Belstrøm, University of Copenhagen
  • ,
  • Christian von Buchwald, University of Copenhagen

BACKGROUND: Hyposalivation and xerostomia (dry mouth), are the leading site-effects to treatment of head and neck cancer. Currently, there are no effective therapies to alleviate radiation-induced hyposalivation. Adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) have shown potential for restoring salivary gland function. However, the mode of action is unknown. The purpose of the present study was therefore to characterize the effect of AT-MSC therapy on the salivary proteome in previously irradiated head and neck cancer patients.

METHODS: Whole saliva was collected from patients with radiation-induced salivary gland hypofunction (n = 8) at baseline, and 120 days after AT-MSC treatment, and from healthy controls (n = 10). The salivary proteome was characterized with mass spectrometry based proteomics, and data was compared within the AT-MSC group (baseline versus day 120) and between AT-MSC group and healthy controls. Significance levels between groups were determined by using double-sided t-test, and visualized by means of principal component analysis, volcano plots and cluster analysis.

RESULTS: Here we show that 140 human proteins are significantly differentially expressed in saliva from patients with radiation-induced hypofunction versus healthy controls. AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment. However, AT-MSC treatment does not restore healthy conditions, as 212 proteins are significantly differentially expressed in saliva 120 days after AT-MSCs treatment, as compared to healthy controls.

CONCLUSION: The results indicate an increase in proteins related to tissue regeneration in AT-MSCs treated patients. Our study demonstrates the impact of AT-MSCs on the salivary proteome, thereby providing insight into the potential mode of action of this novel treatment approach.

Original languageEnglish
Article number160
JournalCommunications medicine
Volume2
Issue1
Number of pages12
ISSN2730-664X
DOIs
Publication statusPublished - Dec 2022

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