Abstract
Background and purpose
Recently, stem cell therapy has been proposed to allow regeneration of radiation damaged
salivary glands. It has been suggested that glial-cell-derived neurotrophic factor
(GDNF) promotes survival of mice salivary gland stem cells (mSGSCs). The purpose of
this study was to investigate the role of GDNF in the modulation of mSGSC response
to irradiation and subsequent salivary gland regeneration.
Methods
Salivary gland sphere derived cells of Gdnf hypermorphic (Gdnfwt/hyper) and wild type mice (Gdnfwt/wt) were irradiated (IR) with γ-rays at 0, 1, 2, 4 and 8 Gy. mSGSC survival and stemness were assessed by calculating surviving fraction measured
as post-IR sphere forming potential and population doublings. Flow cytometry was used
to determine the CD24hi/CD29hi stem cell (SC) population. QPCR and immunofluorescence was used to detect GDNF expression.
Results
The IR survival responses of mSGSCs were similar albeit resulted in larger spheres
and an increased cell number in the Gdnfwt/hyper compared to Gdnfwt/wt group. Indeed, mSGSC of Gdnfwt/hyper mice showed high sphere forming efficiency upon replating. Interestingly, GDNF expression
co-localized with receptor tyrosine kinase (RET) and was upregulated after IR in vitro and in vivo, but normalized in vivo after mSGSC transplantation.
Conclusion
GDNF does not protect mSGSCs against irradiation but seems to promote mSGSCs proliferation
through the GDNF-RET signaling pathway. Post-transplantation stimulation of GDNF/RET
pathway may enhance the regenerative potential of mSGSCs.
Keywords
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Article info
Publication history
Published online: August 04, 2017
Accepted:
July 6,
2017
Received in revised form:
July 6,
2017
Received:
May 1,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
