The use of the oral mucosal model, in place of animal or patient testing, enables us to carry out very much more extensive and exhaustive test programmes. This is ideal for evaluating the biocompatibility of new dental treatments, for example, where we can test complete formulations, plus the components individually and in any combination.
The effect of any treatment can be precisely measured. Commonly we monitor cell histology, plus release of cytokines and inflammatory markers. More in-depth information can be obtained using affinity arrays to characterise gene expression in the model epithelium under control and test conditions. These tests allow us to quickly identify any irritant or toxic components on the basis of the observed changes.
The epithelial model is being used with some success to develop an understanding of oral candidiasis (‘Thrush’). We now know that an invasive, hyphal form of the fungus Candida spp. causes this. We are currently evaluating what factors trigger the conversion from the relatively benign ‘yeast’ form present in most people’s mouths, to the active ‘disease’ form.
Tissue engineered skin and oral mucosa are also being used to develop models of other diseases that affect these tissues. These models allow us to study disease processes and evaluate new treatments without the need for animal experiments.
Right: Micrographs of two sections through the oral mucosal model. The oral mucosal model at the bottom has been treated with an invasive strain of Candida spp.
One of the models we are developing is of an early invasive skin and oral cancer. This project is following the addition of cancerous cells to tissue engineered skin or oral mucosa – producing an in vitro model that we intend will open a way to the development of effective treatments and better early detection of these early cancers.
Later stage tumours, and metastases, form a solid ball of cells that steadily grow in size. We can also model these in vitro by growing tumour spheroids. As the ball of cells grows in size, the center becomes starved of oxygen and nutrients. This causes tumours to release factors that encourage the growth of new blood vessels and also makes them resistant to radio- and chemo-therapy. Using tumour spheroids we can study the interaction of tumours with their surrounding tissues and the immune system as well as developing better methods for targeting treatment at these more advanced tumours.
Above: Movie clip showing the first twenty five days in the life of a breast cancer tumour. After day 6 a dark centre can be seen in the tumour ball. This is where tissue is becomming necrotic due to lack of oxygen and nutrients in the core of the tumour.
Targeted Drug Delivery
We are also using these tissue and disease models to test and develop smart drug delivery systems. By combining our knowledge of tissue specific markers and smart drug encapsulation systems we are developing the means to selectively deliver payloads of genes, radioisotopes and drugs into target cells, such as head and neck cancer cells whilst avoiding other tissues in the body. Using our model systems we can rigorously test the selectivity and effectiveness of these smart drug delivery systems before moving to clinical trials.