Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells

Patients with Sjogren's syndrome (1-2 million in the U.S.), and patients exposed to ionizing radiation during therapy for head and neck cancer (\~40,000 new patients/year in the U.S.), experience severe salivary gland hypofunction. In both patient groups, via different pathogenic mechanisms, acinar cells in the glands are lost. These cells are the sole site of fluid production in salivary glands, and such patients cannot produce adequate levels of saliva, leading to considerable morbidity (xerostomia, dysphagia, dental caries, oro-pharyngeal infections, and mucositis). In many patients, all parenchymal tissue may be lost. For this latter group, there is no available therapy as they are not candidates for either pharmacological or gene therapy if little to no epithelial tissue remains. Recent reports suggest that organ-specific stem cells can differentiate into cells of other organs. These findings carry significant implications for possible clinical use. This protocol will investigate if adult human hematopoietic stem cells (HSC) can transdifferentiate into salivary gland and oral mucosal epithelial cells. We will recruit female bone marrow transplant recipients (from existing NHLBI protocols) who have received HSC from a male donor. This gender-mismatched strategy will allow us to detect cells of donor origin by using an RNA probe specific to the human Y chromosome. A biopsy of labial minor salivary glands and a cheek scraping will be obtained from female transplant patients. The biopsy causes minimal discomfort and the cheek scraping is a non-invasive technique. Both procedures are used routinely for clinical diagnosis. The samples will be co-stained for specific genetic and protein markers for salivary gland or oral mucosal epithelial cells, respectively. Cells positive for these markers (Y chromosome, cytokeratins, mucin 1, and NKCC1) would indicate that the donor's HSC became functionally competent salivary gland epithelial cells. This protocol will also examine bone marrow transplant recipients with chronic Graft-versus-Host Disease (GVHD). These patients show similar complications (xerostomia and oral mucositis) as those encountered in patients with Sjogren's Syndrome. We hypothesize that GVHD may provide a positive recruitment signal for HSC to home to salivary and oral mucosal sites. This protocol will recruit 5 female bone marrow transplant recipients without GVHD and 5 with GVHD. The primary potential benefit of this study is that if HSC can turn into salivary gland cells, they could be used to regenerate lost salivary gland tissues or to seed an artificial salivary gland for patients with irreversible salivary gland damage.