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
Number of pages12
Publication statusPublished - Dec 2022

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