Abstract

This report describes our initial attempt to regenerate salivary glands using induced pluripotent stem (iPS) cells in vivo and in vitro. Glandular tissues that were similar to the adult submandibular glands (SMGs) and sublingual glands could be partially produced by the transplantation of iPS cells into mouse salivary glands. However, the tumorigenicity of iPS cells has not been resolved yet. It is well known that stem cells affect their microenvironment, known as a stem cell niche. We focused on the niche and the interaction between iPS cells and salivary gland cells in our study on salivary gland regeneration. Coculture of embryonic SMG cells and iPS cells have better-developed epithelial structures and fewer undifferentiated specific markers than monoculture of embryonic SMG cells in vitro. These results suggest that iPS cells have a potential ability to accelerate differentiation for salivary gland development and regeneration.

Highlights

  • IntroductionHypofunction of the salivary glands can cause various life-disrupting side effects, such as dental caries, swallowing difficulties, loss of taste, and oral candidiasis

  • Salivary glands have important functions in maintaining oral health [1]

  • Induced pluripotent stem cells can be generated from fully differentiated nonpluripotent cells and possess pluripotency similar to that of embryonic stem (ES) cells [4]. iPS cells could be a powerful tool in regenerative medicine, but their potential tumorigenicity is a significant challenge for clinical use [5, 6]

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Summary

Introduction

Hypofunction of the salivary glands can cause various life-disrupting side effects, such as dental caries, swallowing difficulties, loss of taste, and oral candidiasis. Irradiation therapy and Sjogren’s syndrome can cause salivary gland hypofunction and xerostomia. ES cells and other stem cells have a microenvironment that is self-renewing and have multilineage developmental potential. In vivo, these properties are not autonomous to stem cells, and recent evidence points to a level of external control from the microenvironment that defines the stem cell niche. The stem cell niche may represent a significant entry point for therapeutic modulation of stem cell behavior [7, 8]. It is known that the microenvironment is derived from iPS cells, the niche of iPS cells has not been well studied [9, 10]

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