Dental pulp-derived stem cell-conditioned media attenuates secondary Sjögren's syndrome via suppression of inflammatory cytokines in the submandibular glands

Kenichi Ogata; Mayu Matsumura-Kawashima; Masafumi Moriyama; Tatsuya Kawado; Seiji Nakamura

doi:10.1016/j.reth.2021.01.006

Dental pulp-derived stem cell-conditioned media attenuates secondary Sjögren's syndrome via suppression of inflammatory cytokines in the submandibular glands

Regen Ther. 2021 Feb 9:16:73-80. doi: 10.1016/j.reth.2021.01.006. eCollection 2021 Mar.

Authors

Kenichi Ogata¹, Mayu Matsumura-Kawashima¹, Masafumi Moriyama¹, Tatsuya Kawado¹, Seiji Nakamura¹

Affiliation

¹ Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Abstract

Introduction: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease, which affects the exocrine glands. Its primary symptoms are decreased moisture in the mouth and eyes. Therapies are limited to treatment with steroids, which has unpleasant side effects, so new treatments would be beneficial. One possibility might be stem cells, such as bone marrow mesenchymal stem cells (BMMSCs) or dental pulp-derived stem cells (DPSCs); these have been reported to exert immunomodulatory effects on activated lymphoid cells. This study aimed to evaluate the effects of conditioned media from DPSCs (DPSC-CM) or BMMSCs (BMMSC-CM) on salivary functions in SS.

Methods: Cytokine array analysis was performed to assess the types of cytokines present in the media. DPSC-CM or BMMSC-CM was administered in an SS mouse model. Histological analysis of the salivary glands was performed, and gene expression levels of inflammatory and anti-inflammatory cytokines in the submandibular glands (SMGs) were evaluated.

Results: DPSC-CM contained more anti-inflammatory factors than BMMSC-CM. The mice that were given DPSC-CM had a lower number of inflammation sites in the SMGs than those in the other experimental groups, and their salivary flow rate increased. The expression levels of interleukin (IL)-10 and transforming growth factor-β1 increased in the DPSC-CM group, while those of Il-4, Il-6, and Il-17a decreased. The mice that received DPSC-CM showed a significantly increased percentage of regulatory T cells and a significantly decreased percentage of type T helper 17 cells compared to other groups.

Conclusions: These results indicate that DPSC-CM could be an effective therapy for SS-induced hyposalivation, since it decreases the number of inflammatory cytokines and regulates the local inflammatory microenvironment in the SMGs.

Keywords: Bone marrow mesenchymal stem cells; Dental pulp; Sjögren's syndrome; Submandibular glands.