Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells
Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells
This study will examine whether transplanted stem cells can turn into salivary gland cells in
 stem cell recipients. If so, stem cells might be used to restore salivary gland function in
 patients with Sjogren's syndrome and other causes of dry mouth. People with severe dry mouth
 may develop difficulty swallowing, severe tooth decay, infections of the mouth and pharynx,
 and mouth sores.

 Female patients 18 years of age and older who are enrolled in the National Heart, Lung and
 Blood Institute's protocol 97-H-009 or 97-H-0202 and who have received a stem cell transplant
 from a male donor may be eligible for this study. Five patients with graft-versus host
 disease (GVHD) and five without GVHD will be included. GVHD is a transplantation reaction in
 which the donor's cells mount an immune response against the recipient's tissues. Patients
 with chronic GVHD have mouth ulcerations and dry mouth similar to that of patients with
 Sjogren's syndrome. Five healthy female volunteers will also be enrolled.

 Participants will have a medical and dental history. Then, cells will be collected from the
 inside of the cheek (buccal cell scraping) and from the salivary glands (labial gland biopsy)
 as described below:

 Buccal cell scraping - Cells are collected from the inside of the cheek by wiping for 5
 seconds with a plastic brush.

 Labial glands biopsy - The lower lip will be numbed and a small incision will be made on the
 inside of the lower lip. Six small salivary glands in the lower lip will be removed and the
 incision will be closed with four stitches.

 Cells collected from these procedures will be examined to see if donated stem cells turned
 into salivary gland or cheek cells.

 Patients will return to the clinic 5 to 10 days after the biopsy to have the stitches removed
 and assess healing.
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.
INCLUSION CRITERIA:

 We will review medical records of patients enrolled in NHLBI protocol who are 18 years of
 age or older.

 EXCLUSION CRITERIA:

 This study excludes any subjects younger than 18 years old.

 Female subjects recruited for this study would ideally have no prior history of male
 childbearing or abortion.