Ogata Kenichi, Matsumura-Kawashima Mayu, Moriyama Masafumi, Kawado Tatsuya, Nakamura Seiji
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.
Regen Ther. 2021 Feb 9;16:73-80. doi: 10.1016/j.reth.2021.01.006. eCollection 2021 Mar.
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.
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.
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 and increased in the DPSC-CM group, while those of , , and 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.
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.
干燥综合征(SS)是一种慢性炎症性自身免疫性疾病,会影响外分泌腺。其主要症状是口腔和眼睛的水分减少。治疗方法仅限于使用类固醇,但会产生不良副作用,因此新的治疗方法将是有益的。一种可能性可能是干细胞,如骨髓间充质干细胞(BMMSC)或牙髓来源的干细胞(DPSC);据报道,这些干细胞对活化的淋巴细胞具有免疫调节作用。本研究旨在评估DPSC条件培养基(DPSC-CM)或BMMSC条件培养基(BMMSC-CM)对SS患者唾液功能的影响。
进行细胞因子阵列分析以评估培养基中存在的细胞因子类型。在SS小鼠模型中给予DPSC-CM或BMMSC-CM。对唾液腺进行组织学分析,并评估下颌下腺(SMG)中炎症和抗炎细胞因子的基因表达水平。
DPSC-CM比BMMSC-CM含有更多的抗炎因子。给予DPSC-CM的小鼠SMG中的炎症部位数量低于其他实验组,并且它们的唾液流速增加。DPSC-CM组中 和 的表达水平升高,而 、 和 的表达水平降低。与其他组相比,接受DPSC-CM的小鼠调节性T细胞百分比显著增加,辅助性T细胞17型百分比显著降低。
这些结果表明,DPSC-CM可能是治疗SS引起的唾液分泌减少的有效疗法,因为它可以减少炎症细胞因子的数量并调节SMG中的局部炎症微环境。