Role of Hemotopoietic Stem Cells in Periodontal Ligament Homeostasis

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 DESCRIPTION (provided by applicant): Periodontal disease, a chronic inflammatory disease, can result in irreversible destruction of tissues leading to a loss of attachment between teeth and their supporting tissues. Almost 47.2% adults have some degree of periodontal disease in the US. Current treatments for periodontal disease lack efficacy in promoting the regeneration of the essential structures: alveolar bone, cementum and the periodontal ligament (PDL). Several strategies are being tested experimentally to enhance periodontal regeneration, one of them being the use of stem cells. Identification of suitable cells for seeding into periodontal defects would be a powerful tool to promote regeneration. Recently, studies have shown that PDL cells can be derived from cells in the bone marrow (BM). Using mice transplanted with a clonal population derived from a single enhanced green fluorescent protein+ (EGFP+) hematopoietic stem cell (HSC), data from our lab has demonstrated that the HSCs can give rise to several tissue fibroblasts, adipocyte and osteoblasts. Preliminary data from our lab demonstrates the presence of GFP+ cells in the PDL of GFP- mice transplanted with a clonal population derived from a single EGFP+ HSC. The GFP co-localized with a-smooth muscle actin and osteocalcin, indicating that HSCs may differentiate into fibroblasts and osteoblasts in the PDL. Thus, this proposal is to test the hypothesis that HSCs play a role in the PDL turnover and homeostasis by differentiating into the cells in the PDL and also to identify the factors regulating this differentiation. Aim 1 will determine the relative contribution of HSCs to the PDL, identify the sub-population (s) in the PDL that the HSCs give rise to and determine the participation of the HSCs in the PDL turnover/homeostasis. The goal of Aim 2 is to delineate the factors expressed or secreted by the HSC-derived cells in the PDL and then examine the effect of selected factors on the differentiation/maturation of sorted HSCs in vitro. By the completion of these studies, we will have established and characterized the relative contribution of a novel source of cells, HSCs, to PDL turnover/homeostasis and identified factors (known or new) responsible for generation of the lineages from the HSCs, thereby identifying targets for enhancing HSC-derived cell participation in PDL regeneration. Findings from this study will be significant in tha they can be applied in vivo to enhance healing of the tissue in diseases such as periodontitis through the use of the HSCs. These initial studies will allow us to test this radical hypothesis and obtain sufficient preliminary data for subsequent Research Project Grant (R01) application.