Submandibular Gland

BackgroundOrgan replacement regenerative therapy based on human adult stem cells may be effective for salivary gland hypofunction. However, the generated tissues are immature because the signaling factors that induce the differentiation of human salivary gland stem cells into salivary glands are unknown.MethodsIsolated human submandibular gland stem/progenitor cells (hSMGepiS/PCs) were characterized and three-dimensionally (3D) cultured to generate organoids and further induced by fibroblast growth factor 10 (FGF10) in vitro. The induced spheres alone or in combination with embryonic day 12.5 (E12.5) mouse salivary gland mesenchyme were transplanted into the renal capsules of nude mice to assess their development in vivo. Immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, calcium release analysis, western blotting, hematoxylin-eosin staining, Alcian blue-periodic acid-Schiff staining, and Masson's trichrome staining were performed to assess the structure and function of generated tissues in vitro and in vivo.ResultsThe isolated hSMGepiS/PCs could be long-term cultured with a stable genome. The organoids treated with FGF10 [FGF10 (+) group] exhibited higher expression of salivary gland-specific markers; showed spatial arrangement of AQP5+, K19+, and SMA+ cells; and were more sensitive to the stimulation by neurotransmitters than untreated organoids [FGF10 (-) group]. After heterotopic transplantation, the induced cell spheres combined with mouse embryonic salivary gland mesenchyme showed characteristics of mature salivary glands, including a natural morphology and saliva secretion.ConclusionFGF10 promoted the development of the hSMGepiS/PC-derived salivary gland organoids by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. Moreover, the hSMGepiS/PCs responded to the niche in mouse embryonic mesenchyme and further differentiated into salivary gland tissues with mature characteristics. Our study provides a foundation for the regenerative therapy of salivary gland diseases.

Salivary glands, such as submandibular glands (SMGs), are composed of branched epithelial ductal networks that terminate in acini that together produce, transport and secrete saliva. Here, we show that the transcriptional regulator Yap, a key effector of the Hippo pathway, is required for the proper patterning and morphogenesis of SMG epithelium. Epithelial deletion of Yap in developing SMGs results in the loss of ductal structures, arising from reduced expression of the EGF family member Epiregulin, which we show is required for the expansion of Krt5/Krt14-positive ductal progenitors. We further show that epithelial deletion of the Lats1 and Lats2 genes, which encode kinases that restrict nuclear Yap localization, results in morphogenesis defects accompanied by an expansion of Krt5/Krt14-positive cells. Collectively, our data indicate that Yap-induced Epiregulin signaling promotes the identity of SMG ductal progenitors and that removal of nuclear Yap by Lats1/2-mediated signaling is critical for proper ductal maturation.

BackgroundEvidence in imaging studies suggests that there may be differences in glandular involvement in Sjogren's syndrome (SS) depending on the stage of the disease. No detailed histological studies are available to show if there are any such difference in glandular involvement at various time periods and stages of SS. This cross sectional study examines the inflammatory changes in mouse models of SS at various ages.MethodsThe histological changes in major salivary and lacrimal glands were studied at ages of 3, 6, 9, 12, 15 and 18 months in both sexes in well characterized mouse models of SS, non-obese diabetes mouse and Interleukin-14 alpha-transgenic mice.ResultsOur results indicate that early inflammation concurrently occur in submandibular and lacrimal glands around the age of 6 weeks. Parotid glands are involved much later in the course of SS with less severe inflammation. Sublingual glands are rarely involved.ConclusionsOur conclusions are that SS may be an organ specific disease with early inflammation occurring in submandibular and lacrimal glands, followed by the parotid. Non organ specific events occur in later courses of the disease. The understanding of the disease progression is important in tailoring early local therapeutic interventions before complete destruction of salivary and lacrimal glands.

Achieving optimal neck contour during facial rejuvenation may require addressing the submandibular glands, as supraplatysmal fat removal alone is insufficient for many patients, particularly those with fuller necks. The purpose of this study is to review the rate of complications associated with removal and techniques to improve safety. A comprehensive search was conducted to identify literature on complications associated with submandibular gland removal in the context of facial rejuvenation. Studies were included if they provided patient data and complication rates following surgical outcomes. Screening of 908 articles identified 11 (1.21%) studies on complication rates related to submandibular gland resection for aesthetic purposes. A total of 3379 participants were included, of which 48.86% (n = 1651) underwent submandibular gland resection, with a mean age of 50.4 years (range, 32-83), and 88.53% (n = 247) were female. Complications included hematomas (1.15%, n = 16), requiring reoperation in 23.08% (n = 3) of cases, sialoceles (1.33%, n = 21), salivary fistulas (0.82%, n = 6), nerve injury (3.97%, n = 40), xerostomia (0.13%, n = 1), and neck induration (21.43%, n = 21), with complication rates varying across studies. Submandibular gland reduction offers aesthetic benefits but comes with potential risks. Effective preoperative planning, meticulous gland mobilization, and proper exposure are essential for minimizing risks. Advances in techniques, such as improved dissection methods, the use of botulinum toxin, netting techniques, and energy-based instruments like LigaSure (Medtronic, Minneapolis, MN), have enhanced the safety of the procedure. While complications can arise, they typically resolve within a few months, and the overall outcomes improve with surgical experience. The associated risks and benefit profile should be discussed thoroughly with patients. Level of Evidence: 3 (Therapeutic).