Characterisation of human bronchial epithelial response to injury and identification of potential resident progenitor cells in vitro

Nijmeh, Hala S. (2009) Characterisation of human bronchial epithelial response to injury and identification of potential resident progenitor cells in vitro. PhD thesis, University of Nottingham.

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Abstract

As the first line of defence against external stimuli, the airway epithelium undergoes frequent injury during an adult life. This is countered by repair mechanisms that ensure the integrity of the epithelium. It has been established that there are resident stem/progenitor cells localized within specific niches throughout the respiratory tract. Stem/progenitor cells are activated according to the severity of the insult and are thought to be responsible for repairing the airway epithelium. It has been difficult to isolate those stem cells.

In this study, an in vitro human bronchial epithelial model was adapted and characterised. In culture, a pseudostratified epithelium was observed, with basal, ciliated, and secretory cells. Mucus production was also seen in this model. A scrape-wound of the model was employed to study the responses of the airway epithelium to injury. It was observed that migration and then proliferation, of CD44 expressing basal cells, are the first events that take place after scrape-wounding. Up-regulation of CD44 was also observed at the edge of the wounds early post-wounding. This suggested a key role for CD44-expressing basal cells in migration and proliferation after wounding, also suggesting this population may contain a progenitor cell population.

Investigation of the secretory profile of the airway epithelium post-wounding revealed an increase in a number of cytokines and growth factors. In particular, IL-6, IL-8, ENA-78, and RANTES were all elevated compared with unwounded cultures.

A side population (SP) was identified in differentiated and undifferentiated human bronchial epithelial cells in at least some cultures accounting for 0.1-1.15% of cells present.

In summary, the epithelium is important in airway wound repair with basal cells appearing to contain the progenitor population in this human bronchial epithelial cell (HBEC) model. Moreover, SP studies suggested the presence of SP in at least some cultures, which might contribute to airway regeneration. The secretory profile of the airway epithelium post-wounding indicates up-regulation of specific cytokines, which may be important in the pathogenesis of lung diseases such as asthma and COPD. This model should prove useful to assess wound repair pathways and may be of use in the future for proof of concept studies on novel therapeutic agents.

Item Type:Thesis (PhD)
Supervisors:Hall, I.P.
Uncontrolled Keywords:Bronchi, Epithelial Cells, Epithelium, Stem Cells
Faculties/Schools:UK Campuses > Faculty of Medicine and Health Sciences > School of Clinical Sciences
ID Code:884
Deposited By:Dr. Hala S. Nijmeh
Deposited On:04 Nov 2009 09:32
Last Modified:04 Nov 2009 09:32

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