Atrophy or hypofunction of the salivary gland because of aging or disease causes hyposalivation and has an effect on the quality of life of patients, for example not only dry mouth but deterioration in mastication/deglutition disorder and the status of oral hygiene. Currently conducted therapies for atrophy or hypofunction of the salivary gland in clinical practice are only symptomatic treatments with drugs and artificial saliva, and therefore it is preferable to establish a radical therapy. At this time, as a fundamental investigation, by co-culturing mouse early ES (mEES-6) cells with human salivary gland-derived fibroblasts (hSG-fibro), differentiation of mEES-6 cells to salivary gland cells has been attempted. Also, the possibility of cell engraftment was examined. After identifying the cells which were co-cultured with GFP-transfected mEES-6 cells and hSG-fibro, the cells were transplanted into the submandibular gland of SCID mice, and the degree of differentiation into tissues was examined. The possibility of tissue functional reconstitution from co-cultured cells in a three-dimensional culture system was examined. Our results confirmed that the co-cultured cells expressed salivary gland-related markers and had an ability to generate neo-tissues by transplantation in vivo. Moreover, the cells could reconstitute gland structures in a three-dimensional culture system. By co-culture with hSG-fibro, mEES-6 cells were successfully differentiated into salivary gland cells which were transplantable and have tissue neogenetic ability.

Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros). We examined their potential for transplantation and tissue neogenesis. Following the culture of hBFP-ASCs and hSG-fibros, differentiated cells were transplanted into the submandibular glands of SCID mice, and their degree of differentiation in tissues was determined. We also examined their potential for functional tissue reconstitution using a three-dimensional (3D) culture system. Co-cultured cells expressed salivary-glandrelated markers and generated new tissues following transplantation in vivo. Moreover, cell reconstituted glandular structures in the 3D culture system. In conclusion, coculture of hSG-fibros with hBFP-ASCs led to successful differentiation into salivary gland cells that could be transplanted to generate new tissues.

To examine the pathology of salivary glands that have undergone atrophy or hypofunction due to old age or disease, the duct ligation model is used. This model has been used in studies on the course of glandular parenchyma atrophy and the potential for repair and regeneration. However, the period of ligation was short in most of these studies, and none have examined long-term progress. Therefore, we investigated long-term ligation of the submandibular gland in mice and examined the chronic changes in atrophied salivary glands. The ligation periods were 1, 2 and 3 months, and atrophied salivary glands were resected after each period. Resected glands were examined by histology, immunohistochemistry, RT-PCR, and transmission electron microscopy. Histologically, disappearance of acinar cells and increases in duct-like structures were observed over time in atrophied salivary glands, resulting from long-term submandibular gland main excretory duct ligation. Acinar cell markers (-amylase, aquaporin 5) showed marked weakness in expression after ligation, but expression was still observed after 3 months of ligation. Stem cell markers (c-kit, Sca-1) showed greater expression at 1 month of ligation, compared with controls, but expression subsequently decreased with time. Expression of the precursor cell marker cytokeratin 5 was retained throughout long-term ligation. Atrophied salivary gland tissue resulting from long-term ligation showed increases in specific duct-like structures over time, and the expression of stem cell markers and progenitor cell markers in the area of these structures suggests that the repair capability remained intact.

Sarcoidosis is a systemic inflammatory granulomatous disease that affects multiple organs in the body; however, dysphagia is a relatively rare manifestation at early stages. Dysphagia in sarcoidosis is attributed to many mechanisms, such as mediastinal lymphadenopathy, esophageal or laryngeal involvement, cranial neuropathy, and brainstem infiltration. In this article, we report an extremely rare case with sarcoidosis who presented with dysphagia due to isolated cricopharyngeal myopathy. The 75-year-old woman presented with slowly progressive swallowing difficulty and videofluorography showed insufficient opening of the upper esophageal sphincter. On presentation, she had no cranial nerve or central nervous system impairments. A cricopharyngeal myotomy was performed, and histopathological study revealed a significant inflammatory change with non-necrotizing granulomas within the muscle tissue. We concluded that this was a very rare case of sarcoidosis presenting with localized cricopharyngeal myopathy. Postoperatively, a contracture of the esophageal entrance was successfully released and the dysphagia was alleviated.

Myoepithelioma is an extremely rare condition that accounts for 1–1.5 % of salivary gland tumors. It was formerly regarded as a subtype of pleomorphic adenoma, in which myoepithelial structural components predominated, but was listed as a separate disease entity in the 1991 World Health Organization classification (Seifert in Histological typing of salivary gland tumours. Springer, Berlin, 1991). Its histology is highly varied and recurrence is frequent (El-Naggar et al. in J Larygol Otol 103:1192–1197, 1989), with cases of malignant transformation having been reported (Seifert in Histological typing of salivary gland tumours. Springer, Berlin, 1991; Barnes et al. in Pathology and Genetics of head and neck tumours. IARC Press, Lyon, 2005), making this a difficult tumor to control in many cases. This is thought to be due to the multiple differentiation potential of myoepithelial cells, but the details are unknown. There have been a number of reports of the establishment of cell lines (Shirasuna et al. Cancer. 45:297–305, 1980; Jaeger et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 84:663–667, 1997), but numerous points remain unclear. We established a myoepithelial cell line designated METON, and investigated its characteristics. METON consists of cells with two different morphologies: spindle-shaped cells and epithelial-like cells. Then. we also used single-cell cloning method to establish various subclones (epithelial-like, spindle-like, and mixed epithelial-like/spindle-like cell lines). Among these, pluripotency markers were expressed by the mixed epithelial-like/spindle-like cell lines. The newly established cell line expressing these pluripotency markers will be extremely useful for elucidating the diverse histologies of salivary gland tumors.