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