Expansion of salivary gland stem cells for autologous stem cell transplantation

Oral dryness is a common side effect from irradiation of head and neck cancers. Regeneration of salivary glands (SGs) is the most likely remedy since artificial salivas and optimising irradiation protocols only have limited benefits. In vitro expansion of SG stem cells is key for autologous stem cell transplants since only small amounts of SG tissue can be obtained through biopsies to isolate and grow stem cells. Thus far, enrichment in stem cells has been obtained through in vitro culture of SG tissue in primary spheres known as salispheres. However, salispheres rapidly differentiate in vitro, restricting the potential to expand SG stem cell populations. The aim of this project is to improve the in vitro culture of mouse adult SG stem cells to obtain higher yields required to improve the SG function after radiotherapy.

The project will use a range of transgenic mice using the inducible Cre-LoxP technology to monitor activation of signalling pathways, trace and isolate specific cell lineages, and modulate signalling pathways both in vivo and in salispheres in vitro. The techniques used in this project include state-of-the-art mouse genetics, sphere culture of SG cells, cell sorting by flow cytometry, confocal microscopy and immunostaining. In the first year of the PhD, the student will attend taught courses including Experimental Approaches, Project Design and Stem Cell Biology.

The student will join two research groups with complementary expertises in mouse genetics (Miletich) and in vitro culture of SG stem cells (Carpenter).