Wang Shi-Qin, Wang Yi-Xiang, Hua Hong
1 Department of Oral Medicine, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology , Beijing, China .
2 Department of Oral Surgery, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology , Beijing, China .
Stem Cells Dev. 2017 Aug 15;26(16):1171-1185. doi: 10.1089/scd.2017.0045. Epub 2017 Jun 26.
Sjögren's syndrome (SS) is a systemic autoimmune disease that is characterized by focal lymphocytic infiltration into exocrine organs such as salivary and lacrimal glands, resulting in dry mouth and eyes, and other systemic injuries. There is no curative clinical therapy for SS, and stem cell therapy has shown great potential in this area. The mesenchymal stem cells (MSCs) in the salivary glands of healthy individuals and in patients with SS have not been extensively studied. The aim of this study was to elucidate the characteristics of MSCs from the labial glands of healthy controls and of those from patients with SS to elucidate the related pathogenesis and to uncover potential avenues for novel clinical interventions. Labial glands from patients with SS and healthy subjects were obtained, and MSCs were isolated and cultured by using the tissue adherent method. The MSC characteristics of the cultured cells were confirmed by using morphology, proliferation, colony forming-unit (CFU) efficiency, and multipotentiality, including osteogenic, adipogenic, and salivary gland differentiation. The MSCs from the healthy controls and SS patients expressed characteristic MSC markers, including CD29, CD44, CD73, CD90, and CD105; they were negative for CD34, CD45, and CD106, and also negative for the salivary gland epithelium markers (CD49f and CD117). Labial gland MSCs from both groups were capable of osteogenic and adipogenic differentiation. The CFU efficiency and adipogenic differentiation potential of MSCs were significantly lower in the SS group compared with the healthy controls. Cells from both groups could also be induced into salivary gland-like cells. Real-time polymerase chain reaction and immunofluorescence staining showed that the gene and protein expression of AMY1, AQP5, and ZO-1 in cells from the SS group was lower than that in cells from the healthy group. Thus, MSCs from the labial glands in patients with SS could lack certain characteristics and functions, especially related to salivary secretion. These preliminary data provided insights that could lead to the development of novel therapeutic strategies for the treatment of SS.
干燥综合征（SS）是一种全身性自身免疫性疾病，其特征是局灶性淋巴细胞浸润到唾液腺和泪腺等外分泌器官，导致口干、眼干以及其他全身性损伤。目前尚无针对SS的根治性临床疗法，而干细胞疗法在该领域已显示出巨大潜力。健康个体和SS患者唾液腺中的间充质干细胞（MSC）尚未得到广泛研究。本研究的目的是阐明健康对照者和SS患者唇腺中MSC的特征，以阐明相关发病机制，并探索新的临床干预潜在途径。获取了SS患者和健康受试者的唇腺，采用组织贴壁法分离并培养MSC。通过形态学、增殖、集落形成单位（CFU）效率以及多能性，包括成骨、成脂和唾液腺分化，来确认培养细胞的MSC特征。健康对照者和SS患者的MSC表达特征性的MSC标志物，包括CD29、CD44、CD73、CD90和CD105；它们对CD34、CD45和CD106呈阴性，对唾液腺上皮标志物（CD49f和CD117）也呈阴性。两组的唇腺MSC均能够进行成骨和成脂分化。与健康对照者相比，SS组中MSC的CFU效率和成脂分化潜能显著降低。两组的细胞也都能被诱导分化为唾液腺样细胞。实时聚合酶链反应和免疫荧光染色显示，SS组细胞中AMY1、AQP5和ZO-1的基因和蛋白表达低于健康组细胞。因此，SS患者唇腺中的MSC可能缺乏某些特征和功能，尤其是与唾液分泌相关的特征和功能。这些初步数据为开发治疗SS的新治疗策略提供了思路。
