Therapeutic effects of human amniotic mesenchymal stem cell-derived exosomes on stem cell proliferation in irradiated salivary glands via the Wnt pathway.

Abstract

This study investigated the therapeutic potential of exosomes derived from human amniotic mesenchymal stem cells (hAMSCs-EXO) in enhancing stem cell proliferation and tissue regeneration in salivary glands following radiation-induced injury. 60 rats were randomly assigned to five experimental groups: (1) IR (irradiation followed by phosphate-buffered saline (PBS) injection), (2) XAV 939 (irradiation with subsequent administration of the Wnt signaling pathway inhibitor XAV-939), (3) XAV 939 + EXO (irradiation followed by hAMSCs-EXO and XAV-939), (4) EXO (irradiation followed by hAMSCs-EXO), and (5) Control (non-irradiated with PBS administration). Injections were administered on day 1 post-irradiation. Assessments included serial body weight, histopathology (H&E staining), immunofluorescence, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, stem cell marker expression, and proliferation analysis on days 1, 3, 7, and 14. The EXO group demonstrated notable preservation of salivary gland architecture and significantly increased expression of stem cell markers, relative to other irradiated groups, with marked effects observed by day 7. EdU and Ki67 immunostaining further indicated a significant enhancement in proliferative activity following hAMSCs-EXO treatment. In contrast, administration of XAV-939 alone was associated with reduced proliferation and diminished stem cell marker expression. These findings suggest that hAMSC-derived exosomes promote stem cell proliferation and structural restoration in irradiated salivary gland tissue, potentially through activation of the Wnt signaling pathway.