## 3 Discussion  
The literature documenting follow-up of REPs teeth beyond 18 months is limited, and its long-term effects and full impact in a young patient remain unknown [20]. In this case report, we show the follow up of two cases at 5 years and their respective radiographic and clinical success. Despite the loss of pulp  
Figure 4: Histologic microphotographs of the apical fragment surgical removed during the apical surgery of the Case 2. Histologic sections depict the presence of mineralized tissue with the ordinary structure of a root apex (due to mineralization of the apical papilla): (**A**) small magnification of apical root tip with pulp tissue at the main foramen as well as small foramina (f), surrounded by dentin (d) and cement (c). Fragments of granulation tissue (gt) can be observed on the outside root wall. (**B**) High magnification of the cementum–dentin junction (CDJ) of the main canal showing the connective pulp tissue (p), cementum (c) on the inner portion and dentin (d). (**C**) High magnification of foramina depicting in the central portion the pulp tissue surrounded by dentin (d) on the right upper side and by cement (c) on the lower left side. The dental tubules are show in a transversal section. (**D**) High magnification of the apposition/formative phase during cementum formation. Hematoxylin mineralization granules (**blue arrow**) can be observed on the non-mineralized cementum matrix (cm) and cementoblasts (cb). ( Hematoxylin–eosin, H&E). vitality with the development of a chronic abscess in both presented clinical cases, a successful outcome with the resolution of the symptoms and tooth survival was achieved. As reported on a meta-analysis by [PERSON] et al. [20], corroborated by [PERSON] et al. [21] and [PERSON] et al. [22], the periapical healing and tooth survival after REPs are excellent (above 90%), showing also that periapical pathology resolution after REPs was comparable with treatment with an apical barrier or apexification. In case 1, the progressive and continuous apical root formation can be seen through the follow-up X-rays. This phenomenon might be explained by Hertwig's sheath survival, retaining its ability to perform its role on root development and organization (when the inflammatory process was eliminated), and associated to SCAP survival (source of odontoblasts and thereafter can develop root dentin). Trauma, infection, or iatrogenic factors can be responsible for apical papilla and HERS dislodgement from the main root walls [18]. However, if these two structures stay largely uncompromised, they might continue their development independently of periapical pathology resolution [15]. Case report 2 shows that after the first endodontic treatment (by the previous dentist), the apical fragment of the root was dislodged but continued its development separated from the main root even without the resolution of the apical periodontitis. To the best of our knowledge, [PERSON] et al. [7] were the first to demonstrate that the apical papilla was a reservoir for mesenchymal stem cells (SCAPs) fundamental for root development of immature teeth. It appears that SCAP has the inherent aptitude to survive and thrive in the hypoxic environment due to its niche normally being poorly vascularized, its nutrition relying on passive diffusion from the surrounding tissues [17; 19; 23]. Indeed, periradicular granuloma is a highly vascularized granulomatous tissue and is likely to provide even a greater vascular bed than in normal and non-pathological states. From the same research, investigators affirmed that HERS cells are essential for controlling stem cell differentiation in a complement to cement formation through a process of epithelial-mesenchymal transition in which cells undergo a developmental switch from a polarized epithelial phenotype to a greatly motile mesenchymal phenotype [4]. In addition, it was described that _in vitro_ HERS can promote differentiation of periodontal ligaments stem cells into cement forming cells [24].