# Route of Application and Dose Evaluation of Dental Pulp Stem Cells for the Treatment of Sialadenitis Caused by Sjögren’s Syndrome: A Preclinical Study

**Authors:** Zhihao Du, Lifang Feng, Yu Zhang, Xin Peng, Shan Zhang, Rui Zhao, Jia Lei, Xiaotong Li, Guangyan Yu, Chong Ding

PMC · DOI: 10.3390/biomedicines13051068 · Biomedicines · 2025-04-28

## TL;DR

This preclinical study finds that dental pulp stem cells can treat sialadenitis in a mouse model of Sjögren’s syndrome, with optimal results from a specific administration method and dose.

## Contribution

The study identifies the optimal route and dose of dental pulp stem cells for treating SS-related sialadenitis in a preclinical model.

## Key findings

- DPSC administration increased saliva flow rate and reduced lymphocyte infiltration in NOD mice.
- Perfusion of 2 × 10⁵ DPSCs showed the best therapeutic effects compared to other doses and methods.
- DPSC treatment reduced levels of inflammatory cytokines IFN-γ and TNF-α in glandular tissues.

## Abstract

Background: Sjögren’s syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. In this study, non-obese diabetic (NOD) mice were used as an animal model for studying SS, to evaluate the optimal administration route and dose range of dental pulp stem cells (DPSCs) in the treatment of sialadenitis caused by SS. Methods: Different doses of DPSCs were transplanted into the submandibular glands (SMGs) of 14-week-old NOD mice through two different methods: injection or retrograde perfusion through the catheter orifice into the SMG. At 21 weeks of age, the saliva flow rate (SFR), ectopic lymphocytes, and CD4+ T-cell infiltration were measured. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in the glandular tissues were also quantitatively detected. Results: Compared with untreated and PBS-injected controls, different-dose groups of the two administration methods showed an increased saliva flow rate of NOD mice to varying degrees, reduced infiltration of lymphocytes and CD4+ T cells in the SMG, and decreased IFN-γ/TNF-α levels. Finally, we compared these two administration routes and found that the perfusion of 2 × 105 DPSCs presents good therapeutic effects. Conclusions: DPSC perfusion through the catheter orifice is a simple and effective treatment method, which is worthy of further investigation through clinical trials.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IFNG (interferon gamma), CD4 (CD4 molecule)
- **Diseases:** sialadenitis (MONDO:0006969)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}
- **Diseases:** sicca syndrome (MESH:D012859), diabetic (MESH:D003920), autoimmune disorder (MESH:D001327), Sialadenitis (MESH:D012793), obese (MESH:D009765), NOD (MESH:D020191), Sjögren's Syndrome (MESH:D013132)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12109166/full.md

## References

71 references — full list in the complete paper: https://tomesphere.com/paper/PMC12109166/full.md

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Source: https://tomesphere.com/paper/PMC12109166