Basic Fibroblast Growth Factor Enhances Stemness of Human Stem Cells from the Apical Papilla

Abstract

Introduction Stem cells from the apical papilla (SCAP) are a type of mesenchymal stem cells found in the developing tissue, apical papilla, of immature permanent teeth. Studies have shown that SCAP are likely to be a source of primary odontoblasts that are responsible for the formation of root dentin. Basic fibroblast growth factor (bFGF) is a signaling molecule and pleiotropic growth factor involved in tooth root development, and it promotes proliferation of a variety of cell types. The effects of bFGF on SCAP, however, have not been examined. Methods We investigated the regulatory effects of bFGF on the proliferation and differentiation potential of human SCAP in vitro. Changes in the cell cycle and proliferation, colony-forming unit–fibroblastic formation, alkaline phosphatase (ALP) activity, osteogenic/dentinogenic differentiation, and stem cell gene makers of SCAP, cultured in the presence or absence of bFGF, were evaluated. Results Treatment with 5 ng/mL bFGF significantly increased SCAP proliferation and their colony-forming unit–fibroblastic formation efficiency. The growth factor also increased the expression of STRO-1 and the stem cell gene makers Nanog, Oct4, Sox2, and Rex1 in SCAP. In contrast, bFGF reduced the ALP activity, mineral nodule formation, and the expression of ALP, osteocalcin, bone sialoprotein, and dentin sialophosphoprotein. When SCAP cultures were expanded in the presence of bFGF for 1 week, subsequent stimulation of the osteogenic/dentinogenic condition resulted in enhanced differentiation. Conclusions Under certain conditions, bFGF enhances SCAP stemness by up-regulating stem cell gene expression, increasing proliferation ability, and potentiating differentiation potency.

Proliferation and odontogenic differentiation of BMP2 gene-transfected stem cells from human tooth apical papilla: An in vitro study

“…SCAP expressed mesenchymal stem cell phenotypes, including STRO-1 and CD146, and a specific surface marker, i.e., CD24 (2–5). SCAP are considered the source of odontoblasts, which are responsible for the development of root dentin (3–7).…”

Optimization of treatment with recombinant FGF-2 for proliferation and differentiation of human dental stem cells, mesenchymal stem cells, and osteoblasts

“…As previously reported, FGF-2-induced proliferation in PDL cells reaches a plateau at 10 ng/mL of FGF-2, and FGF-2 treatment had little effect on the proliferative response of gingival epithelium cells in a dosedependent manner (Takayama et al 2002). In addition, 100 ng/mL and 5 ng/mL of FGF-2 had been reported to have the most optimal effect on proliferation in dental pulp cells and apical papilla stem cells, respectively (Shimabukuro et al 2009;Wu et al 2012). These reports and our data suggest that an optimal concentration of FGF-2 on proliferative response might be determined in each individual cell line, although cell proliferation was generally increased in dose-dependent manner.…”

“…1D). Although there have been individual studies on the functions of FGF-2 in various oral cells (Hasegawa et al 2010;Shimabukuro et al 2009;Wu et al 2012), optimized and systematic conditions of treatment with FGF-2 are needed in the study of proliferation and differentiation of various adult stem cells, including oral stem cells. For this purpose, we used two adult stem cell types (hDPSCs and PDLSCs), gingival fibroblasts, two types of MSCs originating from bone marrow and adipose tissue, osteoblastic osteosarcoma cells, and human osteoblasts.…”

“…In addition, it is crucial in tooth morphogenesis and periodontal tissue formation (Madan and Kramer 2005;Wu et al 2012). FGF-2 can also enhance cell growth and calcification of human dental pulp stem cells (hDPSCs) (Shimabukuro et al 2009), and stemness of cells derived from apical papilla and deciduous teeth by upregulating stem cell gene expression (Hasegawa et al 2010;Wu et al 2012). While FGF-mediated stemness induction is known, the effects of FGF-2 on both proliferation and differentiation vary depending on the tissue origin.…”

Dental Pulp Stem Cell Niche

“…In addition, bFGF-based neuronal differentiation of DPSCs occurs via the FGFR and PLCγ intracellular transduction pathways [80]. bFGF increases the stemness gene expression and proliferation of SCAP [81].…”