Administration of growth factors promotes salisphere formation from irradiated parotid salivary glands

Vicky T. Nguyen, Peter Dawson, Qionghui Zhang, Zoey Harris, Kirsten Limesand

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy is to target the tumor, secondary exposure occurs in surrounding normal tissues, such as the salivary glands. As a result, despite successful treatment of the cancer, patients are left with long-term side effects due to direct damage to the salivary glands. The effect is chronic and currently there is no treatment. Stem cells are an attractive therapeutic option for treatment of radiation-induced glandular dysfunction because of the potential to regenerate damaged cell populations and restore salivary gland function. However, limited knowledge about the endogenous stem cell population post irradiation hinders the development for stem cell-based therapies. In this study, an ex vivo sphere formation cell culture system was utilized to assess the self-renewal capacity of cells derived from parotid salivary glands at a chronic time point following radiation. Salivary glands from irradiated mice generate significantly fewer salispheres, but can be stimulated with fetal bovine serum (FBS) to generate an equivalent number of salispheres as unirradiated salivary glands. Interestingly, the number and size of salispheres formed is dependent on the concentration of FBS supplemented into the media. Salispheres derived from irradiated glands and cultured in FBS media were found to contain cells that proliferate and express progenitor and acinar cell markers such as Keratin 5, Keratin 14, Aquaporin 5, and NKCC1. Utilization of insulin-like growth factor (IGF1) injections following radiation treatment restores salivary gland function and improves salisphere generation. These findings indicate that stimulation of these cellular populations may provide a promising avenue for the development of cell-based therapies for radiation-induced salivary gland damage.

Original languageEnglish (US)
Article numbere0193942
JournalPLoS One
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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Parotid Gland
salivary glands
Salivary Glands
growth factors
Intercellular Signaling Peptides and Proteins
Stem cells
Radiation
Radiotherapy
stem cells
fetal bovine serum
radiotherapy
Aquaporin 5
Stem Cells
Keratin-14
Keratin-5
keratin
Somatomedins
Head and Neck Neoplasms
Cell- and Tissue-Based Therapy
Cell culture

ASJC Scopus subject areas

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

Cite this

Administration of growth factors promotes salisphere formation from irradiated parotid salivary glands. / Nguyen, Vicky T.; Dawson, Peter; Zhang, Qionghui; Harris, Zoey; Limesand, Kirsten.

In: PLoS One, Vol. 13, No. 3, e0193942, 01.03.2018.

Research output: Contribution to journalArticle

Nguyen, Vicky T. ; Dawson, Peter ; Zhang, Qionghui ; Harris, Zoey ; Limesand, Kirsten. / Administration of growth factors promotes salisphere formation from irradiated parotid salivary glands. In: PLoS One. 2018 ; Vol. 13, No. 3.
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