Statement: To date, no studies have been conducted to definitely identify stem cells or transient amplifying (TA) cells that reside in the oral cavity. Stem cell division creates two cell types, a memory daughter cell and a transient amplifying cell. TA cells, which are slightly more differentiated than stem cells, serve as a reservoir for wound healing and homeostasis. Identification of either the stem cell or TA cell location(s) will provide a better understanding of normal and abnormal epithelial growth and tissue regeneration in the oral cavity.
Epidermal stem cells are located within the bulge zone of the associated hair follicles and not within the basal cell layer of the overlying epidermis. Skin wounds induce increased mitotic activity of bulge cells during wound repair. As the minor salivary glands of the oral mucosa represent an analogous specialized epithelial site, one of the stem cell pools of the oral mucosa may reside within salivary gland acini.
Study Aim: The purpose of this study was to determine the location(s) of the oral mucosal stem cell pool(s).
Materials and Methods: To address this question, we employed: 1) a murine oral mucosal wound healing model (wounding initiates stem cell proliferation), 2) human oral mucosal biopsies of ulcers overlying minor salivary glands. Immunohistochemical
markers employed were: 1) K15 (primitive keratinocytes), 2) BrdU (thymidine analogue indicative of DNA synthesis), 3) CD34 (a putative epidermal stem cell marker), 4) CD133 (hematopoietic and general stem markers).
Results: Initial studies of ulcerated mucoceles demonstrated K15 positive staining tracking along the salivary gland excretory and merging with the associated basal cell layer of the epithelium. These findings prompted the murine studies that entailed palatal wounding. BrdU in vivo labeling, and timed animal sacrifices to monitor progression of the BrdU stained cells recruited to re-epithelialize the wound. Results of these murine studies showed: 1) BrdU stained cells were detected in both the basal cell layer of the intact epithelium adjacent to the wound as well within underlying salivary gland acini and associated ducts, 2) as time post wounding increased, BrdU positivity was indentified in excretory ducts merging with the overlying basal epithelial cells, 3) K15 positivity was distributed in the majority of basal layer epithelial cells and the peripheral portion of the excretory salivary gland ducts, 4) control mice demonstrated negligible BrdU labeling, which was restricted to the basal layer epithelial cells. Our results confirm that CD34 is not stem cell specific in oral mucosa, as this antibody stained mast cells in the underlying connective tissues. Ongoing studies with more stem cell specific antibodies (CD133) are promising and have indicated focal, punctate positivity within few acinar and basal layer epithelial cells. .
Conclusions: These data imply that selected salivary gland acini are comparable to the bulge zone of the hair follicle and these cells contribute to the oral mucosal stem cell pool. Further, the localization of either of these cell pools may lead to advancements in cancer treatment and help direct chemoprevention.