Objectives: Organs of endodermal origin, such as the liver and the pancreas, have common tissue stem cells. These stem/progenitor cells share common characteristics and transdifferentiate into tissue types of each other. In the salivary gland, there are both cells with endo- and ectoderm origins, and also tissue stem/progenitor cells that can differentiate into hepatic and pancreatic phenotypes. Methods: We isolated salivary gland progenitor cells from digested adult human major salivary glands. For single cell preparation, human salivary glands were digested by collagenase / hyarulonidase, and labeled with anti-human CD49f antibodies. Sorted CD49f positive cells were cultured under serum-free conditions. Results: On type I collagen-coated dishes, a part of cell population with small epithelial shape expanded in a monolayer form. Human salivary gland progenitor cells in the monolayer phase expressed various adhesion molecules such as CD29(integrin beta 1), CD44s(hyaluronate receptor), CD49f(integrin alpha 6). Monolayers of 800 to 1000 human salivary gland progenitor cells formed spheroid bodies with diameters of 100 to 120mm. After 6 to 10 days of spherical culture, these spheroid bodies contained insulin-positive cells in the core zone and glucagon-positive cells in the mantle zone, resembling the normal architecture of Langerhans islets. These pancreatic-hormone producing cells were positively stained with pancreatic and duodenal homeobox gene 1(pdx-1). Spheroid body formation is a selective method of inducing differentiation into a pancreatic endocrine lineage. Conclusions: Human salivary glands may be an alternative source of endodermal progenitors for regenerative medicine of pancreatic diseases.

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