# Different Approaches to the Regeneration of Dental Tissues in Regenerative Endodontics
## 1 Introduction  
Tissue engineering is a fast-growing scientific field connecting the principles of medicine, engineering, and biology to replace, restore, or regenerate tissues damaged or lost due to disease and/or trauma [1, 2]. The result of this approach relies on the essential interplay between stem cells, signaling molecules, and scaffolds; known as the classic tissue engineering triad [1]. Stem cells are defined as highly proliferative, unspecialized cells, which have the ability to differentiation into various other types of cells [3, 4]. Postnatal stem cells have been identified in different body tissues, such as bone marrow, peripheral blood, hair follicles, skin, intestine, adipose tissue, pancreas, and dental tissues [5, 6]. Studies indicate that dental pulp contains five types of mesenchymal stem cells (MSCs) [7], which are noteworthy because of their pluripotent properties and easy method of isolation from exfoliated deciduous teeth [8]. It has been suggested, that dental pulp stem cells have the ability to differ not only into teeth tissues, but that they also have a neuronal and muscular differentiation capacity, and thus may play a key role in the future medical treatment of various diseases [9]. The following sources of stem cells in human dental pulp have been characterized [3, 10, 11]:  
* Dental pulp stem cells (DPSCs): Clonogenic cells with high proliferation potential and long-term self-renewal [11], isolated from permanent third molars in 2000 by [PERSON] et al. They reside within niches in pulp chambers [8] in a stable microenvironment,which depends on the interplay between growth factors, extracellular matrix proteins, receptor molecules, and stem cells [5]. Research has indicated that dental pulp stem cells have the ability to become odontoblast-like cells and generate ectopic dentin in the subcutaneous tissues of immunocompromised mice [12; 13]. Furthermore, it was shown that DPSCs can differentiate into other non-dental cells, such as osteoblasts, odontoblast, chondrocytes (thus, they can produce bone and cartilage tissues), neuron cells, adipocyte, cardiomyocytes, and insulin-secreting Beta cells [5; 14]. * Stem cells from exfoliated deciduous teeth (SHED): Isolated by [PERSON] et al., exhibiting multipotential differentiation properties and increased cell-population doublings in comparison to DPSCs [15]. It is hypothesized that SHED cells have an extensive proliferation ability higher than DPSCs and MSCs derived from bone marrow, due to being a more immature population [16]. * Stem cells from apical papillae (SCAP): MSC-like cells located in the tooth root apex, discovered for the first time by [PERSON] et al. in the apical papilla of human immature permanent teeth [12]. Studies performed in immunocompromised rodents showed the odontogenic potential of SCAP cells when multipotent stem cells were transplanted with hydroxyapatite/tricalcium phosphate particles. The regeneration of pulp-like tissue and dentin structure were observed [17]. According to the conducted scientific studies, it is believed that SCAP cells are involved in the formation of root dentin, as a source of primary odontoblast [18], opposed to DPSCs, which take part in reparative dentin formation, providing replacement odontoblast [19]. It is also hypothesized that a positive result of endodontic treatment of infected immature permanent tooth may be achieved due to the reservoir of SCAP in the apical papilla, and their ability to produce primary odontoblasts involved in apexogenesis [12; 20; 21]. * Periodontal ligament stem cells (PDLSCs): These multipotent cells have the potential to develop into cementoblast-like cells, adipocytes, and chondrogenic cells. In vivo experiments have exhibited PDLSC's capacity to form cementum/PDL-like structures [22; 23]. Therefore, using these cells in periodontal regeneration protocols is being considered [24].