Title

Neurotrophic factor promotes stem cell involved salivary gland regeneration post radiotherapy.

Poster Number

14

Lead Author Affiliation

Biomedical Sciences

Additional Authors

Christina S. Kong, Maximilian Diehn, and Quynh-Thu Le

Introduction

Radiotherapy (RT) for head and neck cancer is the major iatrogenic cause of dry mouth. Dry mouth is a hyposalivation condition that leads to difficulty in speaking, eating, mucosal pain, and enhanced risk of dental and mandibular infection. Current treatments only provide temporary relief of the symptoms. Stem cell transplantation therapy may be a very promising future direction that provides restoration of salivary function.

Purpose

The purpose of the study is to identify the salivary gland stem cells (SSCs) and characterize the molecular pathways underneath the stem cell involved salivary gland regeneration post radiotherapy.

Method

Fluorescence-activated cell sorting (FACS) was performed on BD FacsAria II to identify and enrich the stem cell population from salivary gland. 8-10 weeks male C57Bl/6 mice as SSCs donors. 8-10 weeks female C57Bl/6 mice as recipients. The recipients’ SMGs were irradiated with the rest of the body shielded. Serial stem cell transplantations were performed and saliva was collected. Gene- expression microarray is used to analyze the molecular characteristics of the salivary gland stem cells.

Results

We have identified and characterized a stem cell enriched population from the adult mouse submandibular gland. The c-Kit+/Sca1+/CD24+/lin- salivary gland stem cells (SSCs) demonstrated the highest capacity of proliferation, self-renewal among all the populations isolated. Serial transplantations of the SSCs into the irradiated submandibular glands of post RT mice successfully restored the saliva secretion and significantly improved the functional acini. Gene-expression analysis revealed that glial cell line- derived neurotrophic factor (Gdnf) is highly expressed in the SCCs. GDNF expression was upregulated after RT in the SSCs of both mice and humans. More importantly, administration of GDNF increased the salisphere formation in cultured SSCs, and improved the saliva secretion in post RT mice.

Significance

We have identified GDNF as a trophic factor to promote post RT salivary gland regeneration. The neurotrophic factors may be potential therapeutic drug candidates for management of xerostomia.

Location

DeRosa University Center, Stockton campus, University of the Pacific

Format

Poster Presentation

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Apr 25th, 10:00 AM Apr 25th, 12:00 PM

Neurotrophic factor promotes stem cell involved salivary gland regeneration post radiotherapy.

DeRosa University Center, Stockton campus, University of the Pacific

Radiotherapy (RT) for head and neck cancer is the major iatrogenic cause of dry mouth. Dry mouth is a hyposalivation condition that leads to difficulty in speaking, eating, mucosal pain, and enhanced risk of dental and mandibular infection. Current treatments only provide temporary relief of the symptoms. Stem cell transplantation therapy may be a very promising future direction that provides restoration of salivary function.