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. 2022 May;55(5):517-530.
doi: 10.1111/iej.13721. Epub 2022 Mar 29.

Exosomes derived from stem cells from the apical papilla alleviate inflammation in rat pulpitis by upregulating regulatory T cells

Si Yu  1   2 , Xu Chen  1   2 , Yao Liu  1   2 , Xue Y Zhuang  1   2 , Ao C Wang  1   2 , Xue M Liu  1   2 , Shu Zhu  1   2
Affiliations

Exosomes derived from stem cells from the apical papilla alleviate inflammation in rat pulpitis by upregulating regulatory T cells

Si Yu et al. Int Endod J. 2022 May.

Abstract

Aim: To evaluate the effects of exosomes derived from stem cells from the apical papilla (SCAP-Exos) in rats with experimentally induced pulpitis and the effects of SCAP-Exos on the conversion of regulatory T cells (Tregs) and methylation status of the Foxp3 locus in Tregs in vitro.

Methodology: SCAP-Exos were isolated and identified using transmission electron microscopy, western blotting, and nanoparticle tracking analysis. Lipopolysaccharide was used to experimentally induced pulpitis in rats, and the effects of SCAP-Exos on the rats with pulpitis were detected using haematoxylin-eosin staining and immunofluorescence staining. CD4+ CD25- T cells were treated with different doses of SCAP-Exos, and flow cytometric analysis was used to assess the effects of SCAP-Exos on Treg proliferation and conversion. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the expression of interleukin 10 (IL-10). MethylTarget® technology was used to measure the methylation level of the Foxp3 locus in T cells. The expression levels of ten-eleven-translocation (Tet) 1, Tet2, and Tet3 in T cells were detected by real-time PCR and western blotting.

Results: SCAP-Exos had an elliptical vesicle-like structure with a diameter of approximately 143.7 nm and expressed the exosomal markers Alix and CD9. SCAP-Exo administration increased Treg accumulation in the inflamed dental pulp and alleviated inflammation in the dental pulp in vivo. SCAP-Exos promoted Treg conversion in vitro. Mechanistically, SCAP-Exos promoted Tet2-mediated Foxp3 demethylation to maintain the stable expression of Foxp3.

Conclusions: SCAP-Exos promoted Treg conversion and effectively alleviated inflammation in the dental pulp of rats. This study shows that SCAP-Exos can regulate the local immune microenvironment to favour tissue regeneration, thus providing a potential novel strategy utilising SCAP-Exos as a cell-free approach to treat early inflammation of dental pulp in immature permanent teeth in the clinic.

Keywords: exosomes; immunomodulation; pulpitis; rat experimental pulpitis; regulatory T cells (Tregs); stem cells from the apical papilla (SCAP).

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References

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