CD9/SOX2-positive cells in the intermediate lobe of the rat pituitary gland exhibit mesenchymal stem cell characteristics

Abstract Adult tissue stem cells of the anterior pituitary gland, CD9/SOX2-positive cells, are believed to exist in the marginal cell layer (MCL) bordering the residual lumen of the Rathke’s pouch. These cells migrate from the intermediate lobe side of the MCL (IL-MCL) to the anterior lobe side of the MCL and may be involved in supplying hormone-producing cells. Previous studies reported that some SOX2-positive cells of the anterior lobe differentiate into skeletal muscle cells. These findings suggest that CD9/SOX2-positive cells in the anterior pituitary have mesenchymal stem cell (MSC) properties. To substantiate this hypothesis, we examined whether CD9-positive cells isolated from IL-MCL of adult male rats differentiate into mesenchymal cells, such as endothelial cells, adipocytes, chondrocytes, and osteocytes. Immunohistochemical analysis revealed that the CD9-positive cells were positive for the MSC markers, CD349, CD105, CD271, and CD273 and were detected in the early postnatal period at the boundary between the posterior and intermediate lobes but not in the embryonic period. In addition, some adult tissue stem cells derived from external tissues were positive for both CD9 and MSC markers, indicating that few CD9/SOX2-positive cells in the IL-MCL of the pituitary gland are MSCs that invaded from external tissues during pituitary development in the early postnatal period and exist in the adult tissue stem cells as suppliers of hormone-producing and endothelial cells in the anterior lobe. These finding should have implications for application of CD9/SOX2-positive cells in regenerative therapy of the pituitary.