Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells

Alejandro M. Chibly, Lauren Querin, Zoey Harris, Kirsten Limesand

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction.

Original languageEnglish (US)
Article numbere107893
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 19 2014

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salivary glands
Salivary Glands
stem cells
Labels
Stem Cells
mice
cells
keratin
quality of life
Quality of Life
Keratin-14
Keratin-5
Xerostomia
Preventive Medicine
Radiation
therapeutics
Therapeutics
Head and Neck Neoplasms
Deglutition Disorders
Radio

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells. / Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten.

In: PLoS One, Vol. 9, No. 9, e107893, 19.09.2014.

Research output: Contribution to journalArticle

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