Functional salivary gland regeneration as the next generation of organ replacement regenerative therapy

Oral health is maintained by the coordinated function of many organs including the teeth and salivary glands. Dysfunction of these organs causes many problems, such as dental caries, swallowing dysfunction and periodontal disease. Regenerative therapy for salivary gland tissue repair and whole-salivary gland replacement is currently considered a novel therapeutic concept that may have potential for the full recovery of salivary gland function. Salivary gland tissue stem cells are thought to be candidate cell sources for salivary gland tissue repair therapies. In addition, whole-salivary gland replacement therapy may become a novel next-generation organ regenerative therapy. Almost all organs arise from reciprocal epithelial and mesenchymal interactions of the germ layers. We developed a novel bioengineering method, an organ germ method that can reproduce organogenesis through the epithelial-mesenchymal interaction. A bioengineered salivary gland germ can regenerate a structurally correct salivary gland in vitro, and bioengineered salivary glands successfully secrete saliva into the oral cavity from ducts in the recipient through the reestablishment of the afferent-efferent neural network. The bioengineered salivary gland can also improve the symptoms of xerostomia, such as bacterial infection and swallowing dysfunction. In this review, we describe recent findings and technological developments of salivary gland regenerative therapy.