Stem Cell Regeneration in Endodontics

Vedant Dhatrak^*, Anuja Ikhar, Rushikesh Bhonde and Nutan Dhamdhere

^*Correspondence: Vedant Dhatrak, Department of Endodontics Sharad Pawar Dent Collage, Datta Meghe Institute of Medical Science (Deemed to be University) Sawangi (Meghe) Wardha, Maharashtra, India, Email:

Author info »

Introduction

Enamel, dentin, and cementum are the three hard tissues that make up a tooth. The majority of a tooth's structure is dentin, with enamel and cementum covering the crown and root surfaces, respectively. The dental pulp, which is the only soft connective tissue in a tooth that is surrounded by calcified components, is essential to the tooth's capacity to maintain homeostasis as a viable organ. Dental pulp, on the other hand, is prone to a range of environmental irritants, which can cause injuries and infections. Because its ability to restore itself is limited, this can cause irreversible pulpitis or necrosis as well as dentin genetic disturbance. Pulpotomy, followed by inorganic material filling of the canals, is the conventional treatment for pulp problems, which develop when a tooth becomes irreversibly devitalized, rendering it more susceptible to structural failure and secondary infections [1]. Pulpitis is usually treated by removing the pulp and replacing it with inorganic materials (gutta-percha and sealer cement) during Root Canal Therapy (RCT). Pulpitis is usually treated by removing the pulp and replacing it with inorganic materials (gutta-percha and sealer cement) during Root Canal Therapy (RCT). Patients also lose pulpal reactivity and their ability to detect later infections as a result of hot/cold stimulation. Pulpitis is typically treated with inorganic materials (gutta-percha and sealer cement) during Root Canal Therapy (RCT). Due to coronal leakage or periapical micro leakage, pulp extirpation may leave endodontically treated teeth brittle and prone to postoperative fractures and reinfections [2]. In addition, as a result of hot/cold stimulation, patients lose pulpal sensibility and the ability to detect subsequent infections. A different form of regeneration technique is using regenerative endocon hosts. The transplanted cells are extracted from the host (autologous) or from other people (allogenic) and processed (tissue separation) or cultivated in cultures to enhance their numbers. Stem cells are the key to tissue regeneration in this scenario. For the past ten years, dental pulp stem cells have been found [3,4]. Exogenously transplanted dental stem cells are used to regenerate pulp and dentine in small and big animals [5]. Pulp revascularization in immature permanent teeth can be thought of as a cell-homing strategy for pulp regeneration. It's a two-step regeneration-based therapy for immature teeth with necrotic pulps that's been around for ten years. Before being filled with a blood clot caused by periapical tissue haemorrhage, the root canal system is cleansed with antibiotics or calcium hydroxide (Figure 1) [6,7].

The physiology of dental pulp, as well as the role of pulp stem cells in its development:

Figure 1: The role of pulp stem cells in its development.

Arteries>veins>nerve fibres>fibroblast>macrophage

Nerve fibres, as well as arterial and venous vascular networks, are found in the pulp tissue (left panel). The surrounding pulp stem cells, which cohabit with fibroblasts and macrophages in the dental pulp's "middle panel" and can mature into odontoblasts that coat the dentin wall, are supported by this neurovascular bundle. As a result, pulp stem cells are thought to play a role in tooth formation, pulp tissue homeostasis and injury responses, and dentin-pulp regeneration (right panel) [8].

Literature Review

Function odontoblast precursors, DPSC, and pulp regeneration

 In the face of significant exogenous boosts, such as the expansion of caries injuries and pulpal openness to the oral depression by damage or whole ready, odontoblasts are obliterated, and DPSC may separate into odontoblast-like cells to frame reparative dentin. It's unclear how odontoblast antecedents are enrolled. Previous research suggested that pulpal fibroblasts could be a source of recovered odontoblasts. Pericytes, which are situated near vascular endothelial cells, have been proposed as a source of freshly generated odontoblasts. Recently, a population of mesenchymal immature microorganisms (MSC) was identified from dental mash tissue, and these cells are referred to as DPSC.

Stem cells to enhance their angiogenic and neurogenic properties

The ability of relocated cells to survive in vivo is one of the most significant challenges in tissue creation. To overcome this barrier, a number of techniques have been developed to modify immature microorganisms before to transplantation in order to improve cell durability and engraftment [9]. Emetic modification offers a potential strategy to increase stem cell survival, for example, by overexpressing antiapoptotic genes such as BCl2 or Akt [10,11]. Another possibility is to change the outflow of a disease-related protein, such as dopamine in Parkinson's patients or insulin in diabetics. However, because hereditary modification is a young and developing area, many questions must be answered before clinical applications involving hereditarily modified immature cells can be considered feasible [12]. Because hypoxia is a powerful enhancement for the emission of a variety of trophic variables, preparing foundational microorganisms for transplantation by exposing them to a hypoxic environment could be a useful technique for further developing the undifferentiated organism secretome [13]. In a model of murine hind limb ischemia, hypoxic preconditioning has been shown to enhance cell endurance, paracrine motility, and angiogenic intensity. Because oxygen must be delivered by veins that pass through the teeth relatively narrow apical foramen, oxygen levels in the dental mash are lower when compared to other tissues. The proliferation rate of DPSCs increases when they are cultured in hypoxic circumstances [14]. VEGF expression and migration. Moreover, hypoxia also upregulates VEGF production in SCAPs and cells from the periodontal ligament [15]. These studies all contribute to the beneficial effects of hypoxia preconditioning. However, simulating hypoxia by just adding a pharmaceutical specialist would greatly improve the methodology's reachability. Prolyl Hydroxylase (PHD) inhibitors are used to deal with a group of hypoxia impersonators. PHD inhibitors include cobalt chloride and dimethyloxalylglycine, as well as iron chelators such as hinokitiol, deferoxamine, or Limousine. In dental mash determined cells SCAPs and PDL cells, these PHD inhibitors promote VEGF emission and HIF-1 articulation [16]. And surprisingly in a tooth cut organ culture model. Besides, preconditioned DPSCs and SCAPs likewise upgrade narrow organization arrangement by HUVECs. Moreover, the utilization of hinokitiol-animated DPSCs in a mouse Matrigel plug examine brought about an expanded haemoglobin content and PECAM1 articulation [17]. Taken together, these reports recommend a promising future for the utilization of hypoxic mimicry in planning undeveloped cells for in vivo transplantation. HIF-1� and its downstream targets animate angiogenesis as well as neurogenesis. Consequently, hypoxic preconditioning offers new possibilities as to neuro regeneration. Notwithstanding the promising outcomes utilizing BM-MSCs and undeveloped undifferentiated organisms no reports were observed utilizing preconditioned DSCs for the treatment of neurological issues [18,19].

Function of odontoblast and Dental Pulp Stem Cell (DPSC) in stem cell regeneration

If severe external stimuli are present, odontoblasts are killed, such as progression of caries lesions and lung exposure to the oral cavity as a result of trauma or cavity preparation, and DPSC may convert into odontoblast-like cells are generate in reparative dentin. The method for obtaining odontoblast precursors is unknown. Pulpal fibroblasts were once assumed to be a source of regenerated odontoblasts [20]. Pericytes, which are situated near capillary endothelial cells, may be a source of freshly generated odontoblasts. The Mesenchymal Stem Cells (MSC) from dental pulp tissue has recently been found, and these cells are known as DPSC. Several non-collagenous proteins, such as those in the SIBLING family, cause odontoblasts or pulp cells to differentiate and mineralize, however some have deleterious effects on these processes and periostin. For example, Odontoblastic markers are inhibited in expression. Notch is also a receptor that is involved in the development of a variety of tissues/cells and has a negative impact on osteoblast and odontoblast differentiation. Controlling odontoblast growth is critical for pulp tissue regeneration. DPSC Multipotent dental pulp stem cells can differentiate into osteoblasts, adipocytes, and brain cells, among other things. They were given the label postnatal DPSC after being isolated from the pulp tissue of permanent human teeth. The quick growth rate of these postnatal DPSC was usually used to choose them. However, the DPSC generated with this method are a mixed population rather than "pure" stem cells. DPSC can be isolated utilising CD105 or STRO-1 and a fluorescence-activated cell sorting system. Typical MSC markers were found, despite the fact that the total volume of retrieved cells was small. Filter separation methods employing chemotactic agents such as granulocyte colony stimulating factor have since been developed, allowing for the easy isolation of pure DPSC in huge volumes. In dental pulp cells, three-dimensional spheroid cultures that mimic natural and physiological tissue conditions stimulate odontoblastic and osteoblastic marker expression and nodule formation [21,22].

Clinical findings of functional pulp regeneration

In all cases, creature readings are not appropriate for practical tests, for example, the Electric Mash Test (EPT) mostly used in people. Then again, as immediate confirmation of the vitalized work, the mash ability recovered to continuously expand the base of a juvenile dental neck could be examined, yet this strategy has not been utilized in creatures Assessing the viability of the fundamental micro-organism of mashed potatoes has interceded the recovery of mashed potatoes in a clinical setting and clearly show the utility. Sentence Rephrase Ginger Software and monitored for up to 24 weeks after human MDPSC is implanted in situ (i.e. G-CSF-assem). The researchers found complete puree recovery and dentin disposition in three of the five patients using research based on appealing reverberation imaging and cone pillar figured tomography. In addition, 4 of the 5 patients showed positive responses to EFA after 24 weeks of follow-up, demonstrating the feasibility of recovering mash with neuronal recuperation [23].

Treatment: The results of ex vivo Mixed Lymphocyte Reaction (MLR) experiments provided some of the early evidence that MSCs could actively attenuate immunologic responses. These experiments are based on the fact that when T cells from mononuclear cells of immunologically asymmetrical peripheral blood are united under the right conditions, they multiply rapidly. The addition of MSCs to MLRs suppressed T-cell growth, according to the results of MLR tests. While most cell culture studies confirm by far that such findings are mediated by soluble molecules derived from MSC that do not trigger T-cell. Other routes have been considered. Aggarwal suggested a role for prostaglandin E2 (PGE2) depending on their ability to abler the inhibitory responses with cyclooxygenase 2 (COX-2) inhibitors. Di Nicola et al. used a series of antibody blocking assays to involve the role of Transformation of Beta Growth Factor (TGF) and Hepatocyte Growth Factor (HGF). PGE2 and related substances have resulted in dendritic cells regulating the anti-inflammatory cytokine Interleukin (IL) while reducing release [24]. Pro-inflammatory Tumour Necrosis Factor alpha (TNF) and IL12, according to Aggarwal. This, in turn, triggers a change in the T helpe relationship [25]. Th cells from sub-type Th1 pro-inflammatory to sub-type Th2 anti-inflammatory. This was accompanied by the development of naïve T-cells in immuno. Immunoregulatory T lymphocytes (Treg), resulting in a reduction in the total number of Th lymphocytes. CSMs may also cause inflammatory T lymphocytes die by activating the Fas-Fas ligand axis, according to Akiyama. The PBCs recruited more T cells through a positive feedback loop per second secretion of Monocytic Chemoochtactic Protein 1 (MCP-1). Apoptotic debris from T lymphocytes then activated the phagocytes, causing the release of TGF, causing the creation of naïve T cells. Differentiation into Treg cells that increase systemic immunologic tolerance. Meisel et al. suggested a new mechanism by which the MSC operates. Indoleamine-2,3-Dioxygenase (IDO) catalyse the conversion of tryptophan to kynurenin in a way dependent on gamma interferon. Proliferation of T lymphocytes is suppressed by kynurenin. The IDO antagonist 1-methyl-L-tryptophan was subsequently used to support this mechanism. Waterman et al. noted this temporary activation of Toll-Like Receptor (TLR)3 with polyinosinic-polycytidylic acid may drive MSCs to express increased amounts of IDO and PGE2 in a series of tests (poly I:C). The activity of MSC-mediated IDO has also improved tolerance to kidney allografts in mouse models through a Treg ascending regulatory pathway, suggesting that IDO-mediated immune modulation can occur in vivo. Nitric oxide, galectin-1, and semaphorin-3A have all been identified as MSC-derived modulators of T lymphocyte proliferation; however, nitric oxide has been shown to work only as an MSC modulator in the murine system [26,27].

Discussion

Point to be discussed: Enamel, dentin, and cementum are the three hard tissues that make up a tooth. Preserving important dental pulp with its associated vascular and nerve components. The physiology of dental pulp, as well as the role of pulp stem cells in its development. In the face of significant exogenous boosts, such as the expansion of caries injuries and pulpal openness to the oral depression by damage or hole ready odontoblasts are obliterated, and DPSC may separate into odontoblast-like cells to frame reparative dentin [1,3-5].

Stem Cells to Enhance Their Angiogenic and Neurogenic Properties the ability of relocated cells to survive in vivo is one of the most significant challenges in tissue creation. To overcome this barrier, a number of techniques have been developed to modify immature microorganisms before to transplantation in order to improve cell durability and engraftment [6,7].

Function of odontoblast and Dental Pulp Stem Cell (DPSC) in stem cell regeneration: If severe external stimuli are present, odontoblasts are killed, such as progression of caries lesions and lung exposure to the oral cavity as a result of trauma or cavity preparation, and DPSC may convert into odontoblast-like cells are generate in reparative dentin [16,18,26,27].

Conclusions

Preserving important tooth pulp while treating pulp disorders is one of the toughest tasks in modern dentistry. With the recently developed of stem cell–based regenerative protocols to resolve various clinical deficiencies, the discovery and functional characterization of dental MSOC. Specifically pulverulent stem cells, has widened the therapeutic horizons of regenerative endodontics. Of particular importance is the transplantation of CPSD and SHED. Which were proven to have tremendous ability to induce neuro vascularization, has realized complete in situ pulp regeneration with the crucial achieved achievement of neuro vascularization to fulfil functional recovery. Function of odontoblast and Dental Pulp Stem Cell (DPSC) in stem cell regeneration: If severe external stimuli are present, odontoblasts are killed, such as progression of caries lesions and lung exposure to the oral cavity as a result of trauma or cavity preparation, and DPSC may convert into odontoblast-like cells are generate in reparative dentin.

References

1. Gong T, Heng BC, Lo EC, et al. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy. Stem Cell Int 2016; 9204574.

   [Crossref][Google Scholar][Pubmed]

2. Gronthos S, Brahim J, Li W, et al. Stem cell properties of human dental pulp stem cells. J Dent Res 2002; 81:531-535.

   [Crossref][Google Scholar][Pubmed]

3. Dammaschke T, Steven D, Kaup M, et al. Long term survival of root-canal-treated teeth: a retrospective study over 10 years. J Endod 2003; 29:638–643.

   [Crossref][Google Scholar][Pubmed]

4. Gronthos S, Mankani M, Brahim J, et al. Postnatal human Dental Pulp Stem Cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 97:13625–13630.

   [Crossref][Google Scholar][Pubmed]

5. Huang GT, Yamaza T, Shea LD, et al. Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 2010; 16:605-615.

   [Crossref][Google Scholar][Pubmed]

6. Kim SG, Zheng Y, Zhou J et al. Dentin and dental pulp regeneration by the patientâ??s endogenous cells. Endod Topics 2013; 28:106–117.

   [Crossref][Google Scholar][Pubmed]

7. Thibodeau B, Trope M. Pulp revascularization of a necrotic infected immature permanent tooth: case report and review of the literature. Paediatr Dent 2007; 29:47–50.

   [Google Scholar][Pubmed]

8. Sui B, Chen C, Kou X, et al. Pulp Stem Cell-Mediated Functional Pulp Regeneration. J Dent Res 2019; 98:27-35.

   [Crossref][Googlescholar][Pubmed]

9. Muscari C, Giordano E, Bonafe F, et al. "Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine." J Biomed Sci 2013; 20.

   [Crossref][Google Scholar][Pubmed]

10. Li W, Ma N, L L Ong, et al. "Bcl-2 engineered MSCs inhibited apoptosis and improved heart function." Stem Cell 2007; 25:2118–2127.

    [Crossref][Google Scholar][Pubmed]

11. Noiseux N, Gnecchi M, Lopez-Ilasaca M. et al, "Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation." Mol Therapy 2006; 14:840–850.

    [Crossref][Google Scholar][Pubmed]

12. Phillips MI and Tang YL. "Genetic modification of stem cells for transplantation." Advanced Drug Delivery Reviews 2008; 60:160–172.

    [Crossref][Google Scholar][Pubmed]

13. Baraniak PR, McDevitt TC. "Stem cell paracrine actions and tissue regeneration." Regen Med 2010; 5:121–143.

    [Crossref][Google Scholar][Pubmed]

14. Iida K, Takeda-Kawaguchi T, Tezuka Y. et al "Hypoxia enhances colony formation and proliferation but inhibits differentiation of human dental pulp cells," Arch Oral Bio 2010; 55: 648–654.

    [Crossref][Google Scholar][Pubmed]

15. Motohira H, Hayashi J, Tatsumi J, et al. "Hypoxia and reoxygenation augment bone resorbing factor production from human periodontal ligament cells." J Periodontol 2007; 78:1803–1809.

    [Crossref][Google Scholar][Pubmed]

16. Agis H, Watzek G, Gruber R. "Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor by periodontal fibroblasts," J Period Res 2012; 47:165–173.

    [Crossref][Google Scholar][Pubmed]

17. Kim MK, Park HJ, Kim YD, et al. "Hinokitiol increases the angiogenic potential of dental pulp cells through ERK and p38MAPK activation and hypoxia-inducible factor-1ð?¼ (HIF-1ð?¼) upregulation."Arch Oral Bio 2014; 59:102–110.

    [Crossref][Google Scholar][Pubmed]

18. Wei L, Fraser JL, Lu ZY, et al. "Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats." Neurobiol Dis 2012; 46:635–645.

    [Crossref][Google Scholar][Pubmed]

19. Kim YS, Noh MY, Cho KA, et al. "Hypoxia/reoxygenation preconditioned human bone marrow-derived mesenchymal stromal cells rescue ischemic rat cortical neurons by enhancing trophic factor release." Mol Neurobiol 2015; 52:792–803.

    [Crossref][Google Scholar][Pubmed]

20. Yamamura T. Differentiation of pulpal cells and inductive influences of various matrices with reference to pulpal wound-healing. J Dent Res 1985; 64:530–540.

    [Crossref][Google Scholar][Pubmed]

21. Bloch-Zupan A, Jamet X, Etard C et al. Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects. Am J Hum Genet 2011; 89:773-781.

    [Crossref][Google Scholar][Pubmed]

22. Wang X, Thibodeau B, Trope M, et al. Histologic characterization of regenerated tissues in canal space after the revitalization/revascularization procedure of immature dog teeth with apical periodontitis. J Endod 2010; 36:56–63.

    [Crossref][Google Scholar][Pubmed]

23. Basel D, Steiner RD. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition. Am J Hum Genet 2009; 89:773–781.

    [Crossref][Google Scholar][Pubmed]

24. Christiansen HE, Schwarze U, Pyott SM, et al. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet 2010; 86:389-398.

    [Crossref][Google Scholar][Pubmed]

25. Nakashima M, Iohara K. Mobilized dental pulp stem cells for pulp regeneration: initiation of clinical trial. J Endod 2014; 40:26–32.

    [Crossref][Google Scholar][Pubmed]

26. Sui BD, Hu CH, Liu AQ, et al. Stem cell-based bone regeneration in diseased microenvironments: challenges and solutions. Biomaterials 2017; 10:046.

    [Crossref][Google Scholar][Pubmed]

27. Sui BD, Hu CH, Zheng CX, et al. 2016. Micro environmental views on Mesenchymal Stem Cell Differentiation in Aging. J Dent Res 2016; 95:1333-1340.

    [Crossref][Google Scholar][Pubmed]