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

• Published in: Communications medicine 2022-12, Vol.2 (1), p.160-160, Article 160
• Main Authors: Lynggaard, Charlotte Duch, Jersie-Christensen, Rosa, Juhl, Morten, Jensen, Siri Beier, Grønhøj, Christian, Melchiors, Jacob, Jacobsen, Søren, Møller-Hansen, Michael, Herly, Mikkel, Ekblond, Annette, Kastrup, Jens, Fischer-Nielsen, Anne, Belstrøm, Daniel, von Buchwald, Christian
• Format: Article
• Language: English
• Subjects: 42/100; 631/532/2074; 692/308/153; 692/4028/67/1536; 692/699/3020/3031; 692/699/67/1536; 82/58; Cancer therapies; Exocrine glands; Head & neck cancer; Mass spectrometry; Medicine; Medicine & Public Health; Patient safety; Radiation therapy; Scientific imaging; Stem cells
• ISSN: 2730-664X; 2730-664X
• DOI: 10.1038/s43856-022-00223-3

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. Plain language summary Currently, there are no effective treatments to ease dry mouth, which is a leading long-term side effect of radiation treatment for head and neck cancer. However, treatment with stem cells has shown potential for restoring function of the salivary glands, which are damaged due to radiation. We compared proteins in saliva of previously radiation-treated patients with healthy non-irradiated persons and found differences in the levels of 140 proteins. After stem cell treatment of irradiated patients, we found changes in the salivary content of