and they are especially precursors for cells of the tooth attachment apparatus cells of this tissue structure express typical markers for pdl fibroblast, alveolar osteoblasts, and cementoblasts. when cultivated, dfcs have a morphology that is comparable to that of a fibroblast and express markers such as nestin and stro-1 which are typical markers for dental stem cells. these cells have are highly proliferate and proliferate typically at a higher rate than that of a proliferating bone marrow- derived mesenchymal stem cell. regulation of dfcs the initiation of differentiation is controlled by a number of different extracellular factors, such as growth factors, cell-cell contacts, extracellular matrix, and mechanical loading. these factors coordinate to induce or modulate the process of differentiation into particular functional body cell type. there have been some studies done recently about the differentiation of cultivated dfcs into biomineralising cells. these studies revealed new ways in which the cell differentiation mechanisms work. moreover, information about genome-wide expression profiles was provided by proteomics and transcriptomics with dfcs. these help in showing more clearly the molecular mechanisms in cells. the extracellular signal regulated kinase (erk) pathway was also revealed during the osteogenic differentiation of dfcs by these investigations. the proteomics and transcriptomics identified regulated transcription factors such as sp1 and tp53. these transcription factors were more precisely identified by bioinformatics after the analysis of the proteome. the role of these transcription factors regulate the cell proliferation and differentiation of dfcs. human dental follicle cells are progenitor cells. different studies suggested that osteogenic differentiation of dfcs is controlled by bmp2 and igf2, which are growth factors. however, the influence of bmp2 and igf2 on the differentiation of dfcs has not been analysed in too much depth. there was a study that examined dfcs after the induction of osteogenic differentiation with bmp2, igf2 and a standard osteogenic differentiation medium (odm) with dexamethasone. the alkaline phosphatase activity and the calcium accumulation showed osteogenic differentiation after all treatments, but with the most effective differentiation by odm. furthermore, markers of the process of osteoblast differentiation were much higher up-regulated in bmp2- or igf2-treated cells than in odm-treated cells. to find the reason between these differences, the genome-wide expression profiles were compared at an early differentiation stage. chondroblast markers in bmp2-differentiated cells and general markers for cell differentiation/proliferation in igf2-treated cells were significantly regulated. however, odm-treated dfcs expressed late markers of osteogenic-differentiated dfcs such as the transcription factor zbtb16 that is not expressed in bmp2- or igf2-differentiated cells. therefore, this study shows that osteogenic differentiation of dfcs can be triggered with all tested inducers. however to analyse this mechanism, the transcription factor zbtb16 is a target for further investigations. dlx3, a transcription factor, which is related to the induced bmp2 pathway in osteogenic differentiated dfcs was able to trigger cell viability and the osteogenic differentiation of dfcs via the bmp2/smad1 feedback loop ). dfcs control the proportional amount of all three periodontal tissues, which includes a good balance between the size of the periodontal ligament and the amount of the surrounding cementum and alveolar bone. a high level of periodontal ligament in the periodontium supports the growth of the cementum and the alveolar bone. this is why a soft extracellular matrix supports the osteogenic differentiation of dfcs. the migration capacity of dfcs the migration capacity of dfcs can be histological examined, during this, dfcs demonstrate an extensive migratory capacity for dental mesenchymal stem cells, during the initial stages of tooth root development. when compared with the migration capacity of stem cells from the dental pulp of baby teeth and stem cells from the dental apical papilla (dental neural crest derived progenitor cells, dnc-pcs), dfcs are found to have the highest cell migration velocity. furthermore, dfc migration can be accelerated during cultivation, with the use of growth factors found in the dental hard tissue matrix such as tgf-β or bmp2 which have also been found to be involved in the differentiation of dfcs follicle-derived embryonic neural crest stem cells (fencscs) fencscs are a sub-population of dfcs, however both differ in their in cell migration properties. fenscs express high levels of embryonic stem cell markers (tra1-60, tra1-81, oct-4) and mrna transcripts for nanog and rex-1. they have the ability to differentiate into cells of all three germ layers. some examples include, smooth and skeletal muscle, osteoblasts, neurons, glial cells, and adipocytes and therefore display pluripotency. these cells also have high levels of telomerase activity. a strategy that enables isolation of specific types of stem cells within the dental follicle such as fencscs, is known as fluorescent activated cell sorting. cell culturing is also important to consider understanding cellular morphology. dfcs and fencscs spheroid cell clusters under serum – free cell culture conditions. the choice of adequate cell culture conditions is of great importance for a specific feature of dental stem cells. for example, both dfcs and fencscs form spheroid-like cell clusters under serum-free cell culture conditions. periapical follicle stem cells (pafscs) once the development of the tooth root is completed, the df disappears thus meaning that all cells are considered to be part of the periodontium. prior to this stage, a periapical part of the df attaches to the apex of the developing tooth root and is referred to as periapical follicle. therefore, undifferentiated cells within this tissue are known as periapical dental follicle stem cells (pafscs) and can be isolated from colony forming cells within periapical follicle cell cultures. typical markers expressed within these cells include, cd44 and stro1. both cell migration capacity and cell proliferation capacity of these cells are greater than various types of dental mesenchymal stem cells. pfacs are targets of regenerative dentistry due to their high multipotent differentiation potential within all types of dental tissue. despite the closely related developmental origin of pafscs and dfscs, there is still much to learn about pafscs and how they compare to dfsc. role in regenerative dentistry human dental follicles can be separated from impacted wisdom teeth with undeveloped tooth roots. therefore, undifferentiated ectomesenchymal cells can be isolated from both apical and coronal parts of the human dental follicle. the dental follicle contains various types of multipotent stem cells. they are progenitors for all types of periodontal cells providing a potential cell source for periodontal regeneration.