Anatomy, Biogenesis and Regeneration of Salivary Glands

Abstract

An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients per year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients’ quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland (SMG), which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of three general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy, and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph.

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation

“…Current thinking points to radiation-induced loss of primitive mesenchymal stem-like progenitor cells as well as the loss of acinar cells, both of which may potentially contribute to repopulate the salivary gland, together with decreased parasympathetic innervation and loss of endothelial cells and microvessels as the main causes of irreversible salivary hypofunction (12,15,16,27,(47)(48)(49). Previous studies indicate that progenitor populations that are capable of repopulating and restoring salivary gland function following irradiation reside in the ductal cell compartment (10,27,50).…”

Salivary Gland Cancers: A Survey through History, Classifications and Managements

“…They all have the same architecture; an arborized duct which opens into the oral cavity with secretary end pieces called acini which produce the saliva [1]. A mixed structure of extracellular matrix, myoepithelial cells, myoibroblasts, immune cells, endothelial cells, stromal cells, and nerve ibers surround the acinar cells.…”

“…Submandibular glands secrete the saliva through their main excretory duct, called Wharton's, which opens into the oral cavity under the tongue by the lingual frenum at a structure called the sublingual caruncule. In contrast, sublingual gland has small ducts called ducts of Rivinus and a common duct, Bartholin's duct, which connects with Wharton's duct at the sublingual caruncle [1].…”

“…Postganglionic nerves from the otic and submandibular ganglia provide parasympathetic innervation. Superior cervical ganglion makes sympathetic postganglionic nerves which innervate the glands along blood vessels [1,2]. Facial nerve is closely associated with PG capsule and facial nerve injury resulting in hemifacial paralysis is a major complication of parotid gland surgery.…”

Current trends in salivary gland tight junctions

“…Humans and rodents possess 3 pairs of major salivary glands (parotid, submandibular and sublingual) as well as hundreds of minor salivary glands located throughout the oral cavity. 15 Salivary glands are also classified according to their secretory product. For instance, serous glands produce a watery secretion comprised almost exclusively of proteins, 16 while mucous glands produce a viscous secretion rich in glycoproteins (i.e., mucins).…”