## 3 Undifferentiated Cells (Stem Cells)
### Adult Stem Cells
#### 3.4.4.1 General Information  
Dental tissues are identified as a rich source of stem/progenitor cells, which can be used for TE applications [274]. As previously documented [275], different dental stem/progenitor cells have been characterized and isolated in the human dental tissue including dental pulp stem cells (DPSCs) [276], stem cells from exfoliated deciduous teeth (SHED) [277], periodontal ligament stem cells (PDLSCs) [278], stem cells from apical papilla (SCAP) [279], alveolar bone-derived mesenchymal stem cells (ABMSCs) [280], gingvia-derived MSCs (GMSCs) [281], dental follicle stem/progenitor cells (DFPCs) [282], and tooth germ progenitor cells (TGPCs) [283] (Figure 9). The MSCs of dental tissues instead of progenitors exhibit the minimal characterization criteria for human stem cells well-defined by the International Society for Cellular Therapy (ISCT) [162]. The differentiation of these cells into various cell lineages including hepatocytes [284], osteogenic [285], and neurogenic cells [286] has been confirmed. Among these cells, DPSCs have been extensively studied for use in hard TE [288]. DPSCs were initially isolated and characterized by [PERSON] and his colleagues in 2000 [276]. They found that these cells possess a high proliferation rate and a high level of clonogenicity with the ability to produce densely calcified colonies and bone nodules [289]. DPSCs with these features are suitable candidates for cell-based therapies in orthopedic, oral, and maxillofacial reconstruction [290]. SHED cells are other MSCs, which were first harvested and characterized by [PERSON] et al. from primary dentition systems. Like DPSCs, these cells are highly proliferative with the ability to differentiate into different cell lines [291]. PDLSCs were recognized as the MSCs resident in the perivascular space of the periodontitis and can be obtained from mature periodontal ligaments. [PERSON] et al. in 2004 first isolated these cells from human impacted third molars [278]. Currently, a number of locations are used to isolate these cells including root surface (r-PDLSCs), alveolar bone (a-PDLSCs) [240], deciduous teeth (d-PDLSCs) [292; 293; 294], and permanent teeth (p-PDLSCs) [294]. Compared to the conventional PDLSCs, inflamed PDLSCs (i-PDLSCs) originate from pathological conditions and possess a higher proliferation rate, as well as faster migration, but have a lower osteogenic capacity [295]. Although PDLSCs are suitable cells for TE applications, the big obstacle for using them in autologous transplantation is the inevitable tooth extraction [296]. [PERSON] et al. first introduced SCAPs as a population of stem cells located in the tooth root apex [297]. They showed the stemness characteristic of SCAPs by using histologic, immuno-histochemical, and immuno-cytofluorescence analyses. In terms of cellular functions, it has been demonstrated that the proliferation rate and plasticity of SCAPs are greater than DPSCs in vitro, which makes them a suitable source for cell-based therapies [298]. The first report on the successful isolation of ABMSCs belongs to [PERSON] et al. [280]. This type of cell is similar to other dental-derived MSCs with reference to biological properties such as morphology, which is the ability to adhere to plastic and colony formation [274]. GMSCs are a new population of stem cells obtained from human gingival tissue. Like other MSCs, these cells are capable of clonogenicity, self-renewal, and multipotent differentiation. The GMSCs can be easily isolated from the oral cavity of human or animals via gingivectomy techniques with minimal discomfort [299]. Under an appropriate cell culture medium, these cells may differentiate into cells of all embryo layers [300]. The therapeutic potential  
Figure 9: Various stem cell sources within the oral and maxillofacial region. BMSCs: bone marrow-derived MSCs. DPSCs: dental pulp stem cells. SHED: stem cells from human exfoliated deciduous teeth. PDLSCs: periodontal ligament stem cells. DFSCs: dental follicle stem cells. TGPCs: tooth germ progenitor cells.