With the help of stem cell therapy, the regeneration of damaged salivary glands can be stimulated. This is the result of research by PhD student Isabelle Lombaert. This could significantly improve the quality of life of patients being treated for head and/or throat tumours. Radiotherapy often results in the loss of much of their salivary gland functionality, which can lead to mouth infections, tooth decay, reduced taste and smell sensitivity and hindrances to speech and chewing. Lombaert will be awarded her PhD by the University of Groningen on 16 April 2008.
Each year, about 500,000 patients worldwide are diagnosed with head and/or throat tumours. These patients are mainly treated with radiotherapy, sometimes in combination with surgery and/or chemotherapy. The high doses of radiation needed to destroy the malignant tissue can also damage healthy tissue. In the area of the head and throat, the salivary glands are the organs most sensitive to radiation. Over 64 percent of patients permanently lose the ability to produce saliva.
Adult stem cells
Lombaert investigated the possibility of restarting saliva production after radiation with the help of stem cells. Stem cells are primitive cells that are able to reinvigorate themselves and to differentiate into different types of cells. They are subdivided into embryonic and adult stem cells. This research used adult stem cells from bone marrow and from the salivary glands.
Method one: stimulation
The research was designed to increase the number of stem cells in the salivary glands of mice. Lombaert did this in two different ways. First, she mobilized bone marrow stem cells to the bloodstream. They then proceeded via the bloodstream to the salivary glands damaged by radiation. There they turned out to contribute to the formation of saliva-producing cells (acinic cells). However, differentiation of bone marrow cells into salivary gland cells could not be demonstrated. Thus it is probable that the cells from the bone marrow produce substances that stimulate any salivary gland stem cells that have survived the radiation to form acinic cells.
Method two: transplantation
Lombaert also investigated the possibility of isolating salivary gland stem cells from the salivary gland, cultivating these in a laboratory to form clusters of cells, and then transplanting these clusters ‘back’ into the salivary gland. A certain type of cultivated cell, the c-Kit+ cell, appeared to be able to grow there into salivary gland cells. In some cases normal levels of saliva production were again achieved.
In humans too?
Lombaert not only conducted experimental research with mice, but also investigated the possibilities of isolating stem cells from human salivary glands and cultivating them in the laboratory. This turned out to be possible. Further research is needed to see whether cultivated human stem cells can also grow into saliva-producing cells. If that is possible, it would mean a significant improvement in the quality of life of patients who have lost their salivary gland functionality due to radiation. In addition, the method researched may also be applicable to the regeneration of other types of tissue damaged by radiation.
Curriculum vitae
Isabelle Lombaert (Ghent, 1979) studied Bioengineering Sciences in Ghent, Belgium. She conducted her PhD research at the department of Cell Biology at the University Medical Center Groningen (UMCG), within the research school GUIDE. The research was financed by the Dutch Cancer Society (KWF Kankerbestrijding), the European Union and the pharmaceutical firm Amgen. Lombaert’s supervisors are Prof. G. de Haan and Prof. H. Kampinga. Dr R. Coppes was co-supervisor. After the PhD ceremony, Lombaert will take up a position as researcher at the National Institute of Health in Bethesda (Maryland, USA). The title of her thesis is ‘Regeneration of irradiated salivary glands by stem cell therapy’.
