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

**Authors:** Zhuang-Zhuang Li, Min Zhang, Xue Wang, Hui-Zhong Qi, Yue-Yue Wang, Jia-Yu Cao, Gui-Lin Huang, Ni-Ni Zhang

PMC · DOI: 10.1515/biol-2025-1277 · Open Life Sciences · 2026-02-18

## TL;DR

This study shows that exosomes from human amniotic stem cells help repair radiation-damaged salivary glands by boosting stem cell activity through the Wnt pathway.

## Contribution

The study demonstrates that hAMSC-derived exosomes promote tissue repair in irradiated salivary glands via the Wnt pathway.

## Key findings

- hAMSCs-EXO treatment preserved salivary gland structure and increased stem cell marker expression.
- EdU and Ki67 staining showed enhanced cell proliferation after hAMSCs-EXO treatment.
- XAV-939 reduced proliferation, suggesting the Wnt pathway is involved in the therapeutic effect.

## 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.

## Linked entities

- **Proteins:** Wnt (protein Wnt-2), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Chemicals:** XAV-939 (PubChem CID 135418940), phosphate-buffered saline (PubChem CID 24978514), 5-ethynyl-2′-deoxyuridine (PubChem CID 472172)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Atxn1 (ataxin 1) [NCBI Gene 25049] {aka Sca1}, THY1 (Thy-1 cell surface antigen) [NCBI Gene 7070] {aka CD90, CDw90}, CD34 (CD34 molecule) [NCBI Gene 947], NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, ATXN1 (ataxin 1) [NCBI Gene 6310] {aka ATX1, D6S504E, SCA1}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, KRT14 (keratin 14) [NCBI Gene 3861] {aka CK14, EBS1, EBS1A, EBS1B, EBS1C, EBS1D}, Krt14 (keratin 14) [NCBI Gene 287701] {aka Ka14, Krt1-14}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, WNT3A (Wnt family member 3A) [NCBI Gene 89780], DNASE1 (deoxyribonuclease 1) [NCBI Gene 1773] {aka DNL1, DRNI}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, IFT140 (intraflagellar transport 140) [NCBI Gene 9742] {aka CED5, MZSDS, PKD9, RP80, SRTD9, WDTC2}, Wnt2 (Wnt family member 2) [NCBI Gene 114487] {aka Wnt}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, AXIN1 (axin 1) [NCBI Gene 8312] {aka AXIN, CMDOH, PPP1R49}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, DIP2A (DIP2 acetate--CoA ligase A) [NCBI Gene 23181] {aka C21orf106, DIP2}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}
- **Diseases:** IR (MESH:C537629), diabetic (MESH:D003920), cancer (MESH:D009369), induced (MESH:D000092582), Head and neck malignancies (MESH:D006258), tumor susceptibility gene 101 (MESH:C562694), atrophy (MESH:D001284), hyposalivation (MESH:D014987), radiation injury (MESH:D011832), infectious diseases (MESH:D003141), dental caries (MESH:D003731), glandular injury (MESH:D009375), dysfunction of the salivary glands (MESH:D012466), lethargy (MESH:D053609), weight loss (MESH:D015431)
- **Chemicals:** water (MESH:D014867), IR (MESH:D007495), EDU (MESH:C022811), SDS (MESH:D012967), 5-ethynyl-2'-deoxyuridine (MESH:C031086), copper (MESH:D003300), ethanol (MESH:D000431), Paraffin (MESH:D010232), xylene (MESH:D014992), tamoxifen (MESH:D013629), Triton X-100 (MESH:D017830), pentobarbital (MESH:D010424), polyacrylamide (MESH:C016679), polystyrene (MESH:D011137), BCA (MESH:C047117), lipid (MESH:D008055), paraformaldehyde (MESH:C003043), eosin (MESH:D004801), Tween-20 (MESH:D011136), PBS (MESH:D007854), PVDF (MESH:C024865), 4',6-diamidino-2-phenylindole (MESH:C007293), hydrogen peroxide (MESH:D006861), 1xPBS (-), H&amp;E (MESH:D006371), hematoxylin (MESH:D006416), phosphotungstic acid (MESH:D010772), XAV 939 (MESH:C544261), balsam (MESH:D001453)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** C0105S
- **Cell lines:** hAMSCs — Homo sapiens (Human), Somatic stem cell (CVCL_WG61), 939 — Homo sapiens (Human), Acute intermittent porphyria, Finite cell line (CVCL_W223)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12917546/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917546/full.md

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Source: https://tomesphere.com/paper/PMC12917546