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DPSC-EVs Drive Functional Recovery in Sjögren's Disease by Systemic Immunomodulation.

Tatsuya Kawado1, Kenichi Ogata1,2, Masafumi Moriyama3

  • 1Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

Tissue Engineering. Part A
|February 26, 2026
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Summary

Dental pulp stem cell extracellular vesicles (DPSC-EVs) show promise for Sjögren's disease (SjD). A single DPSC-EV dose improved salivary function and reduced inflammation by modulating immune cells in the spleen.

Keywords:
Sjögren’s diseaseTGF-β/Smad signalingdental pulp stem cellsextracellular vesicles

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Area of Science:

  • Immunology
  • Regenerative Medicine
  • Autoimmune Diseases

Background:

  • Sjögren's disease (SjD) causes salivary gland destruction, with limited palliative treatments.
  • Immunomodulatory therapies are needed for SjD.
  • Extracellular vesicles from dental pulp stem cells (DPSC-EVs) offer a cell-free therapeutic approach.

Purpose of the Study:

  • To investigate the therapeutic efficacy of DPSC-EVs in a mouse model of SjD.
  • To compare DPSC-EVs with bone marrow-derived EVs (BMMSC-EVs).
  • To elucidate the mechanism of DPSC-EV immunomodulation.

Main Methods:

  • Administration of DPSC-EVs and BMMSC-EVs to a nonobese diabetic mouse model of SjD.
  • Assessment of salivary gland function, autoantibodies, and inflammation.
  • Tracking DPSC-EVs in vivo and analyzing macrophage interactions and signaling pathways.

Main Results:

  • DPSC-EVs significantly restored salivary gland function and reduced inflammation and autoantibodies.
  • DPSC-EVs preferentially accumulated in the spleen and were internalized by macrophages.
  • DPSC-EVs induced dual modulation of TGF-β/Smad signaling via TGF-β1 delivery and NEDD4L downregulation.

Conclusions:

  • DPSC-EVs represent a promising cell-free therapy for SjD.
  • The therapeutic effect is mediated by splenic macrophage modulation of TGF-β/Smad signaling.
  • DPSC-EVs offer a potential pathway for clinical translation in SjD treatment.