Neurotrophic factor promotes stem cell involved salivary gland regeneration post radiotherapy.
Poster Number
14
Introduction/Abstract
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
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.
