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1
Earar, Kamel, Mihaela Gabriela Luca, Anamaria Zaharescu, Andrei Iliescu, Silvia Martu, and Alexandru-Andrei Iliescu. "Toward a Putative Paradigm Shift in Direct Pulp Capping?" Revista de Chimie 70, no. 6 (July 15, 2019): 2177–80. http://dx.doi.org/10.37358/rc.19.6.7300.
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Conventionally the cases accepted for direct pulp capping are the inadvertently exposed normal pulps and carious exposures in teeth without apical radiolucency. The recent advances in dental materials, namely the bioceramics, allowed successful vital therapy by direct pulp capping even in young permanent teeth with irreversible pulpitis. The choice of pulp capping material is pivotal in pulp vital therapy of carious exposures as tricalcium silicates shift the balance inflammation-healing toward the regeneration of damaged dentin-pulp complex. Anticipating a reliable outcome, the high anti-inflammatory potential and modulating capacity of cytokines and growth factors proved by bioactive endodontic cements in direct pulp capping should be associated with new molecular diagnostic tests and cautious clinical evaluation. However, it seems that a paradigm shift is expected in the decision of direct pulp capping.
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Okamoto, Motoki, Sayako Matsumoto, Ayato Sugiyama, Kei Kanie, Masakatsu Watanabe, Hailing Huang, Manahil Ali, et al. "Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair." Polymers 12, no. 4 (April 17, 2020): 937. http://dx.doi.org/10.3390/polym12040937.
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Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping.
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Danilovic, Vesna, Vanja Petrovic, Dejan Markovic, and Zoran Aleksic. "Histological evaluation of platelet rich plasma and hydroxiapatite in apexogenesis: Study on experimental animals." Vojnosanitetski pregled 65, no. 2 (2008): 128–34. http://dx.doi.org/10.2298/vsp0802128d.
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Background/Aim. There are very few data about the effects of endogenous growth factors in vital pulp therapy, and still they are often controversial. The aim of the study was to evaluate the effects of platelet rich plasma (PRP) in conjugation with hydroxyapatite (HAP), as pulp capping materials, to root and periodontium formation. Methods. Eight young monkeys (Cercopithecus Aethiops) with permanent dentition and incomplete root formation were involved in this study. After pulpotomy, the pulp lesion was capped with calcium hydroxide (control), hydroxyapatite (experimental group I) or hydroxyapatite in conjugation with PRP (experimental group II). Six months later, the animals were sacrificed, the tissue was removed en block, and prepared for the histological analysis in a routine way. Results. The results of the histological analysis revealed that healing process was characterised by dentin bridge formation, maintained morphological and functional integrity of dental pulp and complete formation of dental root and surrounding periodontium. The inflammatory reaction was scored as mild to moderate, in almost all the samples in all groups, suggesting the biocompatibility of the used materials. Conclusion. Materials used in this study are convenient as capping agents, contributing maintaining the integrity of the pulp tissue and facilitating root and periodontium formation. According to histological data it could be suggested that hydroxyapatite in conjugation with endogenous growth factors, represents superior alternative to other materials used in this study.
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Rahayu, Retno Pudji, Nirawati Pribadi, Ira Widjiastuti, and Nur Ariska Nugrahani. "Combinations of propolis and Ca(OH)2 in dental pulp capping treatment for the stimulation of reparative dentin formation in a rat model." F1000Research 9 (April 29, 2020): 308. http://dx.doi.org/10.12688/f1000research.22409.1.
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Background: Caries in the dental pulp result in inflammation and damage to the pulp tissue. During inflammation of the pulp, various inflammatory mediators and growth factors are released, including IL-8, IL-10, TLR-2, VEGF and TGF-β through the NF-kB pathway. In the present study, therapy for pulpal caries was performed through pulp capping by giving a combination of propolis and calcium hydroxide (Ca(OH)2). This treatment was expected to stimulate the formation of reparative dentin as an anti-inflammatory material to prevent pulp tissue damage. Methods: 28 Wistar rats were divided into four groups and treated with Ca(OH)2 with or without the addition of propolis for either 7 or 14 days. Immunohistochemical examination was used to determine the expression of IL-8, IL-10, TLR-2, VEGF, TGF-β in the four treatment groups. Results: The group treated with a combination of propolis and Ca(OH)2 for 7 days showed that the expression of IL-10, IL-8, TLR-2, VEGF, TGF-β increased significantly compared to the treatment group treated with only Ca(OH)2. The expression of IL-10, TLR-2, TGF-β, VEGF increased in the treatment group treated with propolis and Ca(OH)2 for 14 days, while the expression of IL-8 in the decreased significantly. Conclusions: Administration of a combination of propolis and Ca(OH)2 has efficacy in the pulp capping treatment process because it has anti-bacterial and immunomodulatory properties. The results show that it is able to stimulate the process of pulp tissue repair through increased expression of IL-10, TGF-β, VEGF, TLR -2 and decreased expression of IL-8.
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Gupta, Sweta, Chhavi Sharma, Amit Kumar Dinda, Amiya K. Ray, and Narayan C. Mishra. "Tooth Tissue Engineering: Potential and Pitfalls." Journal of Biomimetics, Biomaterials and Tissue Engineering 12 (February 2012): 59–81. http://dx.doi.org/10.4028/www.scientific.net/jbbte.12.59.
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All over the world a large number of people suffer from tooth diseases like dental caries, tooth abscess, and plaques. Tooth loss or damage, which occurs frequently in our society are generally repaired by applying several conventional methods, such as root-canal treatment, direct pulp capping and dental implants. These methods are quite painful, create damage to the surrounding tooth tissues and also may at times have adverse side-effects. The limitations of the conventional methods can be overcome by applying the concept of tooth tissue engineering. Tooth tissue engineering is the application of biosciences and engineering to regenerate a biofunctional tooth, which can be used to replace the missing tooth or repair the damaged tooth. Tissue engineering involves three key elements - cell, scaffold and growth factors, which interact with each other to regenerate a specific tissue. The success of tissue engineering depends on the proper selection of these three key elements and understanding the interactions among them. To bring us close to the realization of a tissue-engineered tooth, immense progress is going on in understanding how tooth is first developed, and there is a good advancement in tooth regeneration. In this review, “tooth tissue engineering” will be discussed, along with the recent advancements and challenges in bring a biofunctional tooth from laboratory out into clinical use.
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Ilic, Jugoslav, Katarina Radovic, Bozidar Brkovic, Jugoslav Vasic, and Jelena Roganovic. "The diabetic dental pulp repair: involvement of vascular endothelial growth factor and bone morphogenetic protein 2." Srpski arhiv za celokupno lekarstvo, no. 00 (2020): 57. http://dx.doi.org/10.2298/sarh200228057i.
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Introduction/Objective. We aimed to investigate the effects of diabetes mellitus (DM) on rat dental pulp repair by measuring time-dependent changes in expressions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP 2) following direct pulp capping. Methods. Two groups, each of 20 Wistar rats, received either streptozotocin (for DM induction) or the same volume of sterile saline. One week later, the pulp of maxillary and mandibular right incisors in diabetic and nondiabetic groups were exposed and capped with calcium hydroxide in order to provoke reparative response. The levels of VEGF and BMP 2 were determined in the pulp tissue lysates one and seven days after the pulp capping, using enzyme-linked immunosorbent assays. Results. Diabetic state per se increased VEGF level, with a peak at first day after the pulp capping (19.3 ? 0.9 pg/mg, p < 0.001), but did not affect BMP 2 levels. Significant increase of BMP 2 expression was noticed on seventh day in capped pulp, but only in diabetic rat (16.7 ? 1.0 pg/mg, p = 0.001). Positive correlation between VEGF and BMP 2 was found on seventh day following capping, only in diabetic pulp (r = 0.905, p = 0.003). Conclusion. Diabetes-induced increase in VEGF expression reflects changes in the inflammatory phase of pulp repair in DM. Increase in BMP 2 expression suggest that stimulating effect of calcium hydroxide appears seven days after diabetic pulp capping.
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Ilić, Jugoslav. "Diabetes Mellitus And Reparative Response Of Dental Pulp." Stomatoloski glasnik Srbije 63, no. 2 (June 1, 2016): 85–90. http://dx.doi.org/10.1515/sdj-2016-0009.
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Abstract Anatomically, dental pulp is connective tissue and specific microcirculatory system with significant reparatory abilities intending to preserve pulp vitality. Various therapeutic approaches in the treatment of affected pulp may be compromised by various factors leading to treatment failure. Due to microcirculatory system disorders, treatment of affected dental pulp in patients with diabetes mellitus (DM) is additional challenge. The function and levels of growth factors could be altered in various diabetic tissues including dental pulp. Among them are growth factors important for reparative response of the pulp. There are experimental evidences that DM impede dental pulp reparation. Therefore, clinical procedures aiming to preserve vitality of diabetic dental pulp should be applied with caution. The aim of this paper is to present basic factors and parameters that affect reparative response of dental pulp in patients with DM.
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Guerrero-Gironés, Julia, Antonia Alcaina-Lorente, Clara Ortiz-Ruiz, Eduardo Ortiz-Ruiz, María P. Pecci-Lloret, Francisco Javier Rodríguez-Lozano, Carlos M. Martínez, and Antonio José Ortiz-Ruiz. "Melatonin as an Agent for Direct Pulp-Capping Treatment." International Journal of Environmental Research and Public Health 17, no. 3 (February 6, 2020): 1043. http://dx.doi.org/10.3390/ijerph17031043.
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Melatonin plays an essential role in the regulation of bone growth. The actions that melatonin exerts on odontoblasts may be similar to its action on osteoblasts. This research aimed to evaluate the pulp response to melatonin used for direct pulp capping to evaluate the antioxidant effect of melatonin administered orally and its influence on dental pulp. Direct pulp capping was performed on the upper molars of Sprague Dawley rats using melatonin or Mineral Trioxide Aggregate (MTA). The study groups were: MTA; Melatonin; MTA + Melatonin administered orally; and Melatonin + Melatonin administered orally. In the latter two groups, the animals drank water dosed with melatonin ad libitum (10 mg/100 mL). After 30 days, the animals were sacrificed, and 5 ml of blood, the kidneys, and the liver were extracted in order to evaluate oxidative stress using thiobarbituric acid reactive substances testing (TBARS). Fragments of the maxilla containing the study molars were prepared for histological evaluation. The degree of pulp inflammation and pulp necrosis, the presence of reparative dentin and dentin bridging the pulp chamber, the presence and regularity of the odontoblastic layer, and the presence of pulp fibrosis were evaluated. No significant differences were found between the four study groups for any of the studied histological variables. The oral administration of melatonin did not modify the local effects of MTA or melatonin on dental pulp, or reduce basal-level oxidative stress. The effect of melatonin on pulp is similar to that of MTA and may be used as an agent for direct pulp capping.
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Kitamura, Chiaki, Tatsuji Nishihara, Masamichi Terashita, Yasuhiko Tabata, and Ayako Washio. "Local Regeneration of Dentin-Pulp Complex Using Controlled Release of FGF-2 and Naturally Derived Sponge-Like Scaffolds." International Journal of Dentistry 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/190561.
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Restorative and endodontic procedures have been recently developed in an attempt to preserve the vitality of dental pulp after exposure to external stimuli, such as caries infection or traumatic injury. When damage to dental pulp is reversible, pulp wound healing can proceed, whereas irreversible damage induces pathological changes in dental pulp, eventually requiring its removal. Nonvital teeth lose their defensive abilities and become severely damaged, resulting in extraction. Development of regeneration therapy for the dentin-pulp complex is important to overcome limitations with presently available therapies. Three strategies to regenerate the dentin-pulp complex have been proposed; regeneration of the entire tooth, local regeneration of the dentin-pulp complex from amputated dental pulp, and regeneration of dental pulp from apical dental pulp or periapical tissues. In this paper, we focus on the local regeneration of the dentin-pulp complex by application of exogenous growth factors and scaffolds to amputated dental pulp.
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Galler, K. M., R. N. D’Souza, J. D. Hartgerink, and G. Schmalz. "Scaffolds for Dental Pulp Tissue Engineering." Advances in Dental Research 23, no. 3 (June 15, 2011): 333–39. http://dx.doi.org/10.1177/0022034511405326.
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For tissue engineering strategies, the choice of an appropriate scaffold is the first and certainly a crucial step. A vast variety of biomaterials is available: natural or synthetic polymers, extracellular matrix, self-assembling systems, hydrogels, or bioceramics. Each material offers a unique chemistry, composition and structure, degradation profile, and possibility for modification. The role of the scaffold has changed from passive carrier toward a bioactive matrix, which can induce a desired cellular behavior. Tailor-made materials for specific applications can be created. Recent approaches to generate dental pulp rely on established materials, such as collagen, polyester, chitosan, or hydroxyapatite. Results after transplantation show soft connective tissue formation and newly generated dentin. For dentin-pulp-complex engineering, aspects including vascularization, cell-matrix interactions, growth-factor incorporation, matrix degradation, mineralization, and contamination control should be considered. Self-assembling peptide hydrogels are an example of a smart material that can be modified to create customized matrices. Rational design of the peptide sequence allows for control of material stiffness, induction of mineral nucleation, or introduction of antibacterial activity. Cellular responses can be evoked by the incorporation of cell adhesion motifs, enzyme-cleavable sites, and suitable growth factors. The combination of inductive scaffold materials with stem cells might optimize the approaches for dentin-pulp complex regeneration.
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Wei, Fulan, Shuangyan Yang, Hui Xu, Qingyuan Guo, Qi Li, Lihua Hu, Dongxu Liu, and Chunling Wang. "Expression and Function of Hypoxia Inducible Factor-1αand Vascular Endothelial Growth Factor in Pulp Tissue of Teeth under Orthodontic Movement." Mediators of Inflammation 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/215761.
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Orthodontic force may lead to cell damage, circulatory disturbances, and vascular changes of the dental pulp, which make a hypoxic environment in pulp. In order to maintain the homeostasis of dental pulp, hypoxia will inevitably induce the defensive reaction. However, this is a complex process and is regulated by numerous factors. In this study, we established an experimental animal model of orthodontic tooth movement to investigate the effects of mechanical force on the expression of VEGF and HIF-1αin dental pulp. Histological analysis of dental pulp and expressions of HIF-1αand VEGF proteins in dental pulp were examined. The results showed that inflammation and vascular changes happened in dental pulp tissue in different periods. Additionally, there were significant changes in the expression of HIF-1αand VEGF proteins under orthodontic force. After application of mechanical load, expression of HIF-1αand VEGF was markedly positive in 1, 3, 7 d, and 2 w groups, and then it weakened in 4 w group. These findings suggested that the expression of HIF-1αand VEGF was enhanced by mechanical force. HIF-1αand VEGF may play an important role in retaining the homeostasis of dental pulp during orthodontic tooth movement.
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Itoh, Y., J. I. Sasaki, M. Hashimoto, C. Katata, M. Hayashi, and S. Imazato. "Pulp Regeneration by 3-dimensional Dental Pulp Stem Cell Constructs." Journal of Dental Research 97, no. 10 (April 27, 2018): 1137–43. http://dx.doi.org/10.1177/0022034518772260.
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Dental pulp regeneration therapy for the pulpless tooth has attracted recent attention, and clinical trial studies are underway with the tissue engineering approach. However, there remain many concerns, including the extended period for regenerating the dental pulp. In addition, the use of scaffolds increases the risk of inflammation and infection. To establish a basic technology for novel dental pulp regenerative therapy that allows transplant of pulp-like tissue, we attempted to fabricate scaffold-free 3-dimensional (3D) cell constructs composed of dental pulp stem cells (DPSCs). Furthermore, we assessed viability of these 3D DPSC constructs for dental pulp regeneration through in vitro and in vivo studies. For the in vitro study, we obtained 3D DPSC constructs by shaping sheet-like aggregates of DPSCs with a thermoresponsive hydrogel. DPSCs within constructs remained viable even after prolonged culture; furthermore, 3D DPSC constructs possessed a self-organization ability necessary to serve as a transplant tissue. For the in vivo study, we filled the human tooth root canal with DPSC constructs and implanted it subcutaneously into immunodeficient mice. We found that pulp-like tissues with rich blood vessels were formed within the human root canal 6 wk after implantation. Histologic analyses revealed that transplanted DPSCs differentiated into odontoblast-like mineralizing cells at sites in contact with dentin; furthermore, human CD31–positive endothelial cells were found at the center of regenerated tissue. Thus, the self-organizing ability of 3D DPSC constructs was active within the pulpless root canal in vivo. In addition, blood vessel–rich pulp-like tissues can be formed with DPSCs without requiring scaffolds or growth factors. The technology established in this study allows us to prepare DPSC constructs with variable sizes and shapes; therefore, transplantation of DPSC constructs shows promise for regeneration of pulpal tissue in the pulpless tooth.
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Setyabudi, Setyabudi, Devi Eka Juniarti, Ira Widjiastuti, and Maughfirah Shintya Fathori. "THE EFFECT OF CALCIUM HYDROXIDE-PROPOLIS ON THE NUMBER OF MACROFAG CELLS ON THE WISTAR RAT DENTAL WITH PULPA PERFORMANCE." Conservative Dentistry Journal 10, no. 2 (June 30, 2020): 58. http://dx.doi.org/10.20473/cdj.v10i2.2020.58-61.
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Background: Cellular response of dental pulp to existing lesions, caused by infiltration of inflammatory cells that migrate from blood vessels to the site of injury. Macrophages are the cells that most appear when inflammation occurs. Treatment for maintaining pulp tissue vitality is called pulp capping. Calcium hydroxide as a pulp capping material has the ability to trigger the growth of dentin bridges or remineralization, but calcium hydroxide can induce migration and proliferation of inflammatory cells. Currently the field of dentistry is developing propolis as an alternative pulp capping material. That is because propolis has anti-inflammatory properties. Objective: To analyze the effect of the combination of calcium hydroxide-propolis on the number of macrophage cells in the teeth of wistar rats with pulp perforation. Method: This study used 30 samples of Wistar rats which were preparated until perforation and then divided into 3 groups. The first group continued with filling with cention, the second group continued with application of calcium hydroxide and filled with cention, and the third group continued with the application of combination of calcium hydroxide and propolis and then being filledwithcention. Macrophage cell is calculated histopathologically by using compound light microscope on the 3rd day with 400x magnification. Results: The Kruskal-Wallis test results showed significant differences in macrophages after the combination of calcium hydroxide and propolis (p = 0,000). The combined application of calcium hydroxide and propolis showed higher macrophages than the application of calcium hydroxide and the control group. Conclusion: Application of calcium hydroxide - propolis combination was proven increase the number of macrophage cells in Wistar Rats (Rattus Norvegicus) with pulp perforation
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Wu, Si, Yachuan Zhou, Yi Yu, Xin Zhou, Wei Du, Mian Wan, Yi Fan, Xuedong Zhou, Xin Xu, and Liwei Zheng. "Evaluation of Chitosan Hydrogel for Sustained Delivery of VEGF for Odontogenic Differentiation of Dental Pulp Stem Cells." Stem Cells International 2019 (December 19, 2019): 1–14. http://dx.doi.org/10.1155/2019/1515040.
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The pulpotomy with pulp capping is aimed at retaining vital pulp with reparative dentin formation. Vascular endothelial growth factor (VEGF) plays a crucial role in dentin regeneration; however, its constant administrations in the human body is still problematic. Chitosan was widely studied as an effective carrier to deliver bioactive molecules in regenerative medicine. In this study, we conducted a chitosan/β-glycerophosphate (CS/β-GP) hydrogel as a VEGF-sustained release system and explored its effects on dental pulp stem cells (DPSCs). CS/β-GP hydrogel was manufactured using a sol-gel method. SEM assay showed the spongy and porous microstructure of the lyophilized hydrogels. DPSCs cultured in the CS/β-GP hydrogel kept adhesion and vitality. CCK-8 assay tested the promoted proliferation activity of DPSCs on the hydrogel. Besides, the added VEGF protein could continually release from VEGF/CS/β-GP hydrogel. The VEGF/CS/β-GP hydrogel could promote the odontogenic differentiation of DPSCs better than VEGF treatment without hydrogel. Our results suggested that CS/β-GP hydrogel could continually release VEGF and contribute to odontogenic differentiation of DPSCs, thus may become a potential carrier of bioactive molecules in pulp capping therapy.
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Pishbin, Lida, Fatemeh Sadat Sajadi, Maryam Mahmoudi, and Hassan Shahabinejad. "Knowledge and practice of vital pulp therapy in young permanent teeth among general dental practitioners in Kerman, Iran." International Journal of Dental Research 6, no. 1 (April 17, 2018): 29. http://dx.doi.org/10.14419/ijdr.v6i1.9199.
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The dental pulp is the living tissue of the tooth and its vitality is essential for long-term tooth survival. The vitality or non-vitality of the pulp as well as the presence or absences of a radicular pathology determine the type of pulp therapy. The knowledge of the dentist is important in selecting and carrying out a proper complete treatment. Therefore, this study was conducted to assess general dental practitioner`s (GDP) knowledge of indication, methods and prognosis of vital pulp therapy (VPT) for young permanent teeth (YPT).Method A total of 160 GDPs from dental clinics and offices in Kerman participated in this descriptive cross-sectional study. Data were collected using an initial questionnaire consisted of 15 items examining the knowledge and practice of indication, methods and prognosis of VPT for YPT among GDPs. The participants were asked to choose from the provided answers.Result of 160 questionnaires 154 were used for final evaluation.The overall obtained average score of the total items of the questionnaire was 4.53 ± 3.56. There was not any significant correlation between the knowledge of indication, examination, diagnosis, patients selection, effective factors in success of treatment and gender, number of the years since graduation and the university where the degree was obtained for VPT among GDPs. While knowledge of selecting the right materials for pulp-capping was significantly correlated with the number of the years since graduation and the university where the degree was obtained.Conclusion Although GDPs' level of knowledge in regard to VPT is not favorable, the time since graduation and place of education influenced the suitable material selection for pulp capping. Hence, GDPs, who perform pulp therapy , need to keep themselves updated with these procedures.
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Kim, Sunil, Su-Jung Shin, Yunjung Song, and Euiseong Kim. "In VivoExperiments with Dental Pulp Stem Cells for Pulp-Dentin Complex Regeneration." Mediators of Inflammation 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/409347.
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In recent years, many studies have examined the pulp-dentin complex regeneration with DPSCs. While it is important to perform research on cells, scaffolds, and growth factors, it is also critical to develop animal models for preclinical trials. The development of a reproducible animal model of transplantation is essential for obtaining precise and accurate datain vivo.The efficacy of pulp regeneration should be assessed qualitatively and quantitatively using animal models. This review article sought to introducein vivoexperiments that have evaluated the potential of dental pulp stem cells for pulp-dentin complex regeneration. According to a review of various researches about DPSCs, the majority of studies have used subcutaneous mouse and dog teeth for animal models. There is no way to know which animal model will reproduce the clinical environment. If an animal model is developed which is easier to use and is useful in more situations than the currently popular models, it will be a substantial aid to studies examining pulp-dentin complex regeneration.
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Xie, Zhuo, Zongshan Shen, Peimeng Zhan, Jiayu Yang, Qiting Huang, Shuheng Huang, Lingling Chen, and Zhengmei Lin. "Functional Dental Pulp Regeneration: Basic Research and Clinical Translation." International Journal of Molecular Sciences 22, no. 16 (August 20, 2021): 8991. http://dx.doi.org/10.3390/ijms22168991.
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Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.
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Derringer, K. A., and R. W. A. Linden. "Angiogenic growth factors released in human dental pulp following orthodontic force." Archives of Oral Biology 48, no. 4 (April 2003): 285–91. http://dx.doi.org/10.1016/s0003-9969(03)00008-6.
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Zainal Ariffin, Shahrul Hisham, Shabnam Kermani, Intan Zarina Zainol Abidin, Rohaya Megat Abdul Wahab, Zulham Yamamoto, Sahidan Senafi, Zaidah Zainal Ariffin, and Mohamad Abdul Razak. "Differentiation of Dental Pulp Stem Cells into Neuron-Like Cells in Serum-Free Medium." Stem Cells International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/250740.
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Dental pulp tissue contains dental pulp stem cells (DPSCs). Dental pulp cells (also known as dental pulp-derived mesenchymal stem cells) are capable of differentiating into multilineage cells including neuron-like cells. The aim of this study was to examine the capability of DPSCs to differentiate into neuron-like cells without using any reagents or growth factors. DPSCs were isolated from teeth extracted from 6- to 8-week-old mice and maintained in complete medium. The cells from the fourth passage were induced to differentiate by culturing in medium without serum or growth factors. RT-PCR molecular analysis showed characteristics ofCd146+,Cd166+, andCd31−in DPSCs, indicating that these cells are mesenchymal stem cells rather than hematopoietic stem cells. After 5 days of neuronal differentiation, the cells showed neuron-like morphological changes and expressed MAP2 protein. The activation ofNestinwas observed at low level prior to differentiation and increased after 5 days of culture in differentiation medium, whereasTub3was activated only after 5 days of neuronal differentiation. The proliferation of the differentiated cells decreased in comparison to that of the control cells. Dental pulp stem cells are induced to differentiate into neuron-like cells when cultured in serum- and growth factor-free medium.
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Kaufman, Gili, and Drago Skrtic. "N-Acetyl Cysteine Modulates the Inflammatory and Oxidative Stress Responses of Rescued Growth-Arrested Dental Pulp Microtissues Exposed to TEGDMA in ECM." International Journal of Molecular Sciences 21, no. 19 (October 3, 2020): 7318. http://dx.doi.org/10.3390/ijms21197318.
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Dental pulp is exposed to resin monomers leaching from capping materials. Toxic doses of the monomer, triethyleneglycol dimethacrylate (TEGDMA), impact cell growth, enhance inflammatory and oxidative stress responses, and lead to tissue necrosis. A therapeutic agent is required to rescue growth-arrested tissues by continuing their development and modulating the exacerbated responses. The functionality of N-Acetyl Cysteine (NAC) as a treatment was assessed by employing a 3D dental pulp microtissue platform. Immortalized and primary microtissues developed and matured in the extracellular matrix (ECM). TEGDMA was introduced at various concentrations. NAC was administered simultaneously with TEGDMA, before or after monomer addition during the development and after the maturation stages of the microtissue. Spatial growth was validated by confocal microscopy and image processing. Levels of inflammatory (COX2, NLRP3, IL-8) and oxidative stress (GSH, Nrf2) markers were quantified by immunoassays. NAC treatments, in parallel with TEGDMA challenge or post-challenge, resumed the growth of the underdeveloped microtissues and protected mature microtissues from deterioration. Growth recovery correlated with the alleviation of both responses by decreasing significantly the intracellular and extracellular levels of the markers. Our 3D/ECM-based dental pulp platform is an efficient tool for drug rescue screening. NAC supports compromised microtissues development, and immunomodulates and maintains the oxidative balance.
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Alqahtani, Q., S. H. Zaky, A. Patil, E. Beniash, H. Ray, and C. Sfeir. "Decellularized Swine Dental Pulp Tissue for Regenerative Root Canal Therapy." Journal of Dental Research 97, no. 13 (August 1, 2018): 1460–67. http://dx.doi.org/10.1177/0022034518785124.
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In the current theme of dental pulp regeneration, biological and synthetic scaffolds are becoming a potential therapy for pulp revitalization. The goal is to provide a suitable environment for cellular infiltration, proliferation, and differentiation. The extracellular matrix (ECM) represents a natural scaffold material resembling the native tissue chemical and mechanical properties. In the past few years, ECM-based scaffolds have shown promising results in terms of progenitor cells recruitment, promotion of constructive remodeling, and modulation of host response. These properties make ECM-derived scaffolds an ideal candidate for pulp regenerative therapy. Development of strategies for clinically relevant tissue engineering using dental pulp extracellular matrix (DP-ECM) can provide an alternative to conventional root canal treatment. In this work, we successfully decellularized ECM derived from porcine dental pulp. The resulting scaffold was characterized using immunostaining (collagen type I, dentin matrix protein 1, dentin sialoprotein, and Von Willebrand factor) and enzyme-linked immunosorbent assay (transforming growth factor β, vascular endothelial growth factor, and basic fibroblast growth factor) for extracellular proteins where the ECM retained its proteins and significant amount of growth factors. Furthermore, a pilot in vivo study was conducted where the matrix was implanted for 8 wk in a dog root canal model. Our in vitro and preliminary in vivo data show that the decellularized ECM supports cellular infiltration together with the expression of pulp-dentin and vascular markers (DSP and CD31) compared to the controls. Herein, we show the feasibility to produce a decellularized ECM scaffold and validate the concept of using ECM-based scaffolds for pulp regeneration.
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Rombouts, C., T. Giraud, C. Jeanneau, and I. About. "Pulp Vascularization during Tooth Development, Regeneration, and Therapy." Journal of Dental Research 96, no. 2 (October 11, 2016): 137–44. http://dx.doi.org/10.1177/0022034516671688.
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The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The pulp vascular system is not only responsible for nutrient supply and waste removal but also contributes actively to the pulp inflammatory response and subsequent regeneration. This review discusses the underlying mechanisms of pulp vascularization during tooth development, regeneration, and therapeutic procedures, such as tissue engineering and tooth transplantation. Whereas the pulp vascular system is established by vasculogenesis during embryonic development, sprouting angiogenesis is the predominant process during regeneration and therapeutic processes. Hypoxia can be considered a common driving force. Dental pulp cells under hypoxic stress release proangiogenic factors, with vascular endothelial growth factor being one of the most potent. The benefit of exogenous vascular endothelial growth factor application in tissue engineering has been well demonstrated. Interestingly, dental pulp stem cells have an important role in pulp revascularization. Indeed, recent studies show that dental pulp stem cell secretome possesses angiogenic potential that actively contributes to the angiogenic process by guiding endothelial cells and even by differentiating themselves into the endothelial lineage. Although considerable insight has been obtained in the processes underlying pulp vascularization, many questions remain relating to the signaling pathways, timing, and influence of various stress conditions.
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El karim, Ikhlas A., Gerard J. Linden, Chris R. Irwin, and Fionnuala T. Lundy. "Neuropeptides Regulate Expression of Angiogenic Growth Factors in Human Dental Pulp Fibroblasts." Journal of Endodontics 35, no. 6 (June 2009): 829–33. http://dx.doi.org/10.1016/j.joen.2009.03.005.
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CABRERA, S., D. BARDEN, M. WOLF, and D. LOBNER. "Effects of growth factors on dental pulp cell sensitivity to amalgam toxicity." Dental Materials 23, no. 10 (October 2007): 1205–10. http://dx.doi.org/10.1016/j.dental.2006.11.003.
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Limjeerajarus, Chalida Nakalekha, Narumol Kreua-Ongarjnukool, Sonntana Seang, Prasit Pavasant, and Saowapa Thumsing Niyomthai. "Characterization of a Thermo-Sensitive Injectable Hydrogel as an Iloprost Delivery System for Dental Use." Key Engineering Materials 856 (August 2020): 391–98. http://dx.doi.org/10.4028/www.scientific.net/kem.856.391.
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Iloprost increases the expression of angiogenic factors and increases dental pulp flow, suggesting the potential of iloprost as a biomolecule to promote dental pulp regeneration. However, the methods to clinically deliver iloprost into the limited root canal area of a tooth and control its release are limited. The purpose of this study was to prepare a thermo-sensitive injectable hydrogel from pluronic F127 (PF127) for delivering iloprost to induce dental pulp regeneration. The PF127 hydrogels were fabricated using thermal crosslinking. The maximum cumulative release iloprost from the hydrogel at 25°C was 60%. No significant cytotoxicity or morphological changes were observed in human dental pulp cells (HDPCs) at any of the PF127 gel concentrations of the iloprost carrier. Moreover, the effect of the 20%wt PF127 gels containing iloprost on the expression of VEGF in HDPCs increased vascular endothelial growth factor (VEGF) gene expression at 72 h. The thermo-sensitive hydrogel at 20%wt PF127 containing iloprost could be used for prolonged drug release in dental applications.
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Bergenholtz, G. "Evidence for Bacterial Causation of Adverse Pulpal Responses in Resin-Based Dental Restorations." Critical Reviews in Oral Biology & Medicine 11, no. 4 (October 2000): 467–80. http://dx.doi.org/10.1177/10454411000110040501.
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The widespread use of resin and resin-monomers for bonding of dental restorations to dentin has occurred because of a fundamental shift in the view that injury to the pulp is induced by restorative procedures. While, for many years, the toxic effects of restorative materials were thought to be of crucial importance in the development of adverse pulpal responses the key role of bacterial leakage at the restoration-tooth interface is now well-recognized. Consequently, if optimal conditions for the preservation of pulpal health are to be ensured, dental restorations should provide an impervious seal against the surrounding tooth structure. However, polymerization shrinkage and contraction stresses induced during setting, as well as a variety of technical difficulties encountered during the clinical operation, often produce less than perfect results. Therefore, modern restorative procedures involving resin and resin-bonded restoratives must still rely on the ability of the pulp to cope with the injurious elements to which it may be exposed during and after the procedure. This review examines factors that may govern the pulp's response to restorative procedures that involve adhesive technologies. An assessment is made of the risks involved as far as the continued vital function of the pulp is concerned. It is concluded that an intact, although thin, wall of primary dentin often enables the pulp to overcome both toxic material effects and the influences of bacterial leakage. In contrast, the pulp may not do equally well following capping of open exposures with resin composites. A dearth of controlled clinical studies in this area of dentistry calls for confirmation that pulpal health prevails over the long term following the use of total-etch and resin-bonding techniques.
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Li, Mengjie, Xiaoli Hu, Xiaolan Li, Shuxiang Lei, Ming Cai, Xi Wei, and Dongmei Deng. "Dentist-related factors influencing the use of vital pulp therapy: a survey among dental practitioners in China." Journal of International Medical Research 47, no. 6 (April 16, 2019): 2381–93. http://dx.doi.org/10.1177/0300060519843406.
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Objective To evaluate dentist-related factors associated with the use of vital pulp therapy (VPT) for the treatment of pulp exposures in permanent teeth. Methods This survey-based study sent an online questionnaire to collect data on the demographics of the respondents, the use of VPT and the choice of materials for VPT, to all members of the Society of Endodontology of Guangdong, China. Results A total 183 of 380 members responded (48.2%). The majority (89.6%; 164 of 183) had performed direct pulp capping (DPC) while 55.2% (101 of 183) had performed partial pulpotomy (PP) at least once. The most-cited reason for not performing VPT was unfamiliarity with the technique. Mineral trioxide aggregate was the most commonly used material for both DPC (67.1%; 110 of 164) and PP (73.3%; 74 of 101). Endodontists, compared with general practitioners, preferred to perform DPC and chose calcium silicate materials (CSMs) for VPT (odds ratios 5.81 and 8.07, respectively). DPC and CSMs for VPT were also favoured more by respondents who had practised for > 5 years. Senior respondents were more likely to use PP. Conclusions Speciality, years of practise and age of dentists influenced the decision making and the choice of materials for VPT. Continuing education is essential to promote the clinical use of VPT.
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Jin, Runze, Guangtai Song, Jihua Chai, Xiaohui Gou, Guohua Yuan, and Zhi Chen. "Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro." Journal of Tissue Engineering 9 (January 2018): 204173141881750. http://dx.doi.org/10.1177/2041731418817505.
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Concentrated growth factor, a novel autologous plasma extract, contained various growth factors which promoted tissue regeneration. In this study, we aimed to investigate the biological effects of concentrated growth factor on human dental pulp stem cells. The microstructure and biocompatibility of concentrated growth factor scaffolds were evaluated by scanning electron microscopy. Cell proliferation and migration, odontoblastic and endothelial cell differentiation potential were assessed after exposing dental pulp stem cells to different concentrations (5%, 10%, 20%, 50%, or 80%) of concentrated growth factor extracts. The results revealed that concentrated growth factor scaffolds possessed porous fibrin network with platelets and leukocytes, and showed great biocompatibility with dental pulp stem cells. Higher cell proliferation rates were detected in the concentrated growth factor–treated groups in a dose-dependent manner. Interestingly, in comparison to the controls, the low doses (<50%) of concentrated growth factor increased cell migration, alkaline phosphatase activity, and mineralized tissue deposition, while the cells treated in high doses (50% or 80%) showed no significant difference. After stimulating cell differentiation, the expression levels of dentin matrix protein-1, dentin sialophosphoprotein, vascular endothelial growth factor receptor-2 and cluster of differentiation 31 were significantly upregulated in concentrated growth factor–supplemented groups than those of the controls. Furthermore, the dental pulp stem cell–derived endothelial cells co-induced by 5% concentrated growth factor and vascular endothelial growth factor formed the most amount of mature tube-like structures on Matrigel among all groups, but the high-dosage concentrated growth factor exhibited no or inhibitory effect on cell differentiation. In general, our findings confirmed that concentrated growth factor promoted cell proliferation, migration, and the dental pulp stem cell–mediated dentinogenesis and angiogenesis process, by which it might act as a growth factor–loaded scaffold to facilitate dentin–pulp complex healing.
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El Ashiry, Eman A., Najlaa M. Alamoudi, Mahmoud K. El Ashiry, Hagar A. Bastawy, Douaa A. El Derwi, and Hazem M. Atta. "Tissue Engineering of Necrotic Dental Pulp of Immature Teeth with Apical Periodontitis in Dogs: Radiographic and Histological Evaluation." Journal of Clinical Pediatric Dentistry 42, no. 5 (January 1, 2018): 373–82. http://dx.doi.org/10.17796/1053-4625-42.5.9.
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Aim: To evaluate tissue engineering technology to regenerate pulp-dentin like tissues in pulp canals of immature necrotic permanent teeth with apical periodontitis in dogs. Study design: The study was performed on 36 teeth in 12 dogs. The experiment was carried out using split mouth design. In each dog 3 teeth were selected for implementing the study procedure. Apical periodontitis was induced in Group A and B teeth. Group (A): immature upper left 2nd permanent incisors that were transplanted with a construct of autologous dental pulp stem cells with growth factors seeded in a chitosn hydrogel scaffold. Group (B): immature upper right 2nd permanent incisor that received only growth factors with scaffold. A third tooth in each dog was selected randomly for isolation of dental pulp stem cells (DPSCs). Both groups were closed with a double coronal seal of white MTA (Mineral trioxide aggregate) and glass ionomer cement. Both groups were monitored radiographically for 4 months and histologically after sacrificing the animals. Results: There was no statistically significant difference in radiographic findings between group (A) and group (B) for healing of radiolucencies, while there was statistically significant difference between group (A) and group (B) regarding radicular thickening, root lengthening and apical closure. Histologically, group (A) teeth showed regeneration of pulp- dentin like tissue while group (B) teeth did not show any tissue regeneration. Conclusion: Dental pulp stem cells and growth factors incorporated in chitosan hydrogel are able to regenerate pulp- dentine like tissue and help in complete root maturation of non-vital immature permanent teeth with apical periodontitis in dogs.
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Tete, Stefano, Filiberto Mastrangelo, Anna Paola Scioletti, Michelangelo Tranasi, Florina Raicu, Michele Paolantonio, Liborio Stuppia, et al. "Microarray expression profiling of human dental pulp from single subject." Clinical & Investigative Medicine 31, no. 2 (April 1, 2008): 55. http://dx.doi.org/10.25011/cim.v31i2.3364.
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Introduction: Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Methods: Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. Results: The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. Conclusion: We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.
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Casagrande, Luciano, Letícia Grando Mattuella, Fernando Borba de Araujo, and Jacques Eduardo. "Stem Cells in Dental Practice: Perspectives in Conservative Pulp Therapies." Journal of Clinical Pediatric Dentistry 31, no. 1 (September 1, 2007): 25–27. http://dx.doi.org/10.17796/jcpd.31.1.t744533472930135.
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Stem cells are undifferentiated cells that have the capacity to self-renew. They have been discovered in many adult tissues, including teeth. The Dental Pulp Stem Cells are involved in dentinal repair by activation of growth factors, released after caries process and have the ability to regenerate the dentin-pulp-like complex. The molecular/cellular research raises the possibilities to grow new tissues and biological structures for clinical application, providing cells for therapies including cell transplantation and tissue engineering.
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Tawfik Tadros, Mary Sabry, Maha Abd-El Salam El-Baz, and Mohamed Adel Ezzat Khairy Khairy. "Dental stem cells in tooth repair: A systematic review." F1000Research 8 (November 22, 2019): 1955. http://dx.doi.org/10.12688/f1000research.21058.1.
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Background: Dental stem cells (DSCs) are self-renewable teeth cells, which help maintain or develop oral tissues. These cells can differentiate into odontoblasts, adipocytes, cementoblast-like cells, osteoblasts, or chondroblasts and form dentin/pulp. This systematic review aimed to summarize the current evidence regarding the role of these cells in dental pulp regeneration. Methods: We searched the following databases: PubMed, Cochrane Library, MEDLINE, SCOPUS, ScienceDirect, and Web of Science using relevant keywords. Case reports and non-English studies were excluded. We included all studies using dental stem cells in tooth repair whether in vivo or in vitro studies. Results: Dental pulp stem cell (DPSCs) is the most common type of cell. Most stem cells are incorporated and implanted into the root canals in different scaffold forms. Some experiments combine growth factors such as TDM, BMP, and G-CSF with stem cells to improve the results. The transplant of DPSCs and stem cells from apical papilla (SCAPs) was found to be associated with pulp-like recovery, efficient revascularization, enhanced chondrogenesis, and direct vascular supply of regenerated tissue. Conclusion: The current evidence suggests that DPSCs, stem cells from human exfoliated deciduous teeth, and SCAPs are capable of providing sufficient pulp regeneration and vascularization. For the development of the dental repair field, it is important to screen for more effective stem cells, dentine releasing therapies, good biomimicry scaffolds, and good histological markers.
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Hilkens, Petra, Annelies Bronckaers, Jessica Ratajczak, Pascal Gervois, Esther Wolfs, and Ivo Lambrichts. "The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration." Stem Cells International 2017 (2017): 1–14. http://dx.doi.org/10.1155/2017/2582080.
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Adequate vascularization, a restricting factor for the survival of engineered tissues, is often promoted by the addition of stem cells or the appropriate angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAPs) were applied in an in vivo model of dental pulp regeneration in order to compare their regenerative potential and confirm their previously demonstrated paracrine angiogenic properties. 3D-printed hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously transplanted into immunocompromised mice. After twelve weeks, histological and ultrastructural analysis demonstrated the regeneration of vascularized pulp-like tissue as well as mineralized tissue formation in all stem cell constructs. Despite the secretion of vascular endothelial growth factor in vitro, the stem cell constructs did not display a higher vascularization rate in comparison to control conditions. Similar results were found after eight weeks, which suggests both osteogenic/odontogenic differentiation of the transplanted stem cells and the promotion of angiogenesis in this particular setting. In conclusion, this is the first study to demonstrate the successful formation of vascularized pulp-like tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the promising role of this approach in dental tissue engineering.
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Bergamo, Mariel Tavares, Luciana Lourenço Ribeiro Vitor, Thiago José Dionísio, Nádia Carolina Teixeira Marques, Rodrigo Cardoso Oliveira, Eloá Cristina Passucci Ambrosio, Vivien Thiemy Sakai, et al. "Could the photobiomodulation therapy induce angiogenic growth factors expression from dental pulp cells?" Lasers in Medical Science 36, no. 8 (April 1, 2021): 1751–58. http://dx.doi.org/10.1007/s10103-021-03291-4.
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Todorovic, Vera, Dejan Markovic, Nadezda Milosevic-Jovcic, Marijana Petakov, Bela Balint, Miodrag Colic, Ana Milenkovic, Ivana Colak, Vukoman Jokanovic, and Nebojsa Nikolic. "Dental pulp stem cells: Potential significance in regenerative medicine." Serbian Dental Journal 55, no. 3 (2008): 170–79. http://dx.doi.org/10.2298/sgs0803170t.
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To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.
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Kuramoto, Hitomi, Kouji Hirao, Hiromichi Yumoto, Yuki Hosokawa, Tadashi Nakanishi, Daisuke Takegawa, Ayako Washio, Chiaki Kitamura, and Takashi Matsuo. "Caffeic Acid Phenethyl Ester (CAPE) Induces VEGF Expression and Production in Rat Odontoblastic Cells." BioMed Research International 2019 (December 21, 2019): 1–12. http://dx.doi.org/10.1155/2019/5390720.
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Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries. CAPE significantly induced mRNA expression and production of VEGF in rat clonal odontoblast-like KN-3 cells cultured in normal medium or osteogenic induction medium. CAPE treatment enhanced nuclear factor-kappa B (NF-κB) transcription factor activation, and furthermore, the specific inhibitor of NF-κB significantly reduced VEGF production. The expression of VEGF receptor- (VEGFR-) 2, not VEGFR-1, was up regulated in KN-3 cells treated with CAPE. In addition, VEGF significantly increased mineralization activity in KN-3 cells. These findings suggest that CAPE might be useful as a novel biological material for the dental pulp conservative therapy.
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Moreira, Maria Stella, Giovanna Sarra, Giovanna Lopes Carvalho, Flavia Gonçalves, Hector Valentin Caballero-Flores, Ana Clara Fagundes Pedroni, Cesar Angelo Lascala, Luiz Henrique Catalani, and Márcia Martins Marques. "Physical and Biological Properties of a Chitosan Hydrogel Scaffold Associated to Photobiomodulation Therapy for Dental Pulp Regeneration: An In Vitro and In Vivo Study." BioMed Research International 2021 (January 25, 2021): 1–10. http://dx.doi.org/10.1155/2021/6684667.
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Background. The regeneration of dental pulp, especially in cases of pulp death of immature teeth, is the goal of the regenerative endodontic procedures (REPs) that are based on tissue engineering principles, consisting of stem cells, growth factors, and scaffolds. Photobiomodulation therapy (PBMT) showed to improve dental pulp regeneration through cell homing approaches in preclinical studies and has been proposed as the fourth element of tissue engineering. However, when a blood clot was used as a scaffold in one of these previous studies, only 30% of success was achieved. The authors pointed out the instability of the blood clot as the regeneration shortcoming. Then, to circumvent this problem, a new scaffold was developed to be applied with the blood clot. The hypothesis of the present study was that an experimental injectable chitosan hydrogel would facilitate the three-dimensional spatial organization of endogenous stem cells in dental pulp regeneration with no interference on the positive influence of PBMT. Methods. For the in vitro analysis, stem cells from the apical papilla (SCAPs) were characterized by flow cytometry and applied in the chitosan scaffold for evaluating adhesion, migration, and proliferation. For the in vivo analysis, the chitosan scaffold was applied in a rodent orthotopic dental pulp regeneration model under the influence of PBMT (660 nm; power output of 20 mW, beam area of 0.028 cm2, and energy density of 5 J/cm2). Results. The scaffold tested in this study allowed significantly higher viability, proliferation, and migration of SCAPs in vitro when PBMT was applied, especially with the energy density of 5 J/cm2. These results were in consonance to those of the in vivo data, where pulp-like tissue formation was observed inside the root canal. Conclusion. Chitosan hydrogel when applied with a blood clot and PBMT could in the future improve previous results of dental pulp regeneration through cell homing approaches.
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Mullane, E. M., Z. Dong, C. M. Sedgley, J. C. C. Hu, T. M. Botero, G. R. Holland, and J. E. Nör. "Effects of VEGF and FGF2 on the Revascularization of Severed Human Dental Pulps." Journal of Dental Research 87, no. 12 (December 2008): 1144–48. http://dx.doi.org/10.1177/154405910808701204.
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The long-term outcome of replanted avulsed permanent teeth is frequently compromised by lack of revascularization, resulting in pulp necrosis. The purpose of this study was to evaluate the effects of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) on the revascularization of severed human dental pulps. Tooth slices were prepared from non-carious human molars and treated with 0–50 ng/mL rhVEGF165 or rhFGF-2 for 7 days in vitro. Both angiogenic factors enhanced pulp microvessel density compared with untreated controls (p < 0.05). Tooth slices were also treated with 0 or 50 ng/mL rhVEGF165 for one hour prior to implantation into the subcutaneous space of immunodeficient mice. Treatment with rhVEGF165 increased pulp microvessel density in vivo (p < 0.05). These results demonstrate that rhVEGF165 enhanced neovascularization of severed human dental pulps and suggest that topical application of an angiogenic factor prior to replantation might be beneficial for the treatment of avulsed teeth.
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Chouaib, Batoul, Pierre-Yves Collart-Dutilleul, Nicolas Blanc-Sylvestre, Richard Younes, Csilla Gergely, Cédric Raoul, Frédérique Scamps, Frédéric Cuisinier, and Olivier Romieu. "Identification of secreted factors in dental pulp cell-conditioned medium optimized for neuronal growth." Neurochemistry International 144 (March 2021): 104961. http://dx.doi.org/10.1016/j.neuint.2021.104961.
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Goldberg, M. "Pulp Healing and Regeneration." Advances in Dental Research 23, no. 3 (June 15, 2011): 270–74. http://dx.doi.org/10.1177/0022034511405385.
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Differences between pulp repair and regeneration guide different strategic options. After mild carious dentin lesions, odontoblasts and Hoehl’s cells are implicated in the formation of reactionary dentin. Reparative dentin formation and/or pulp regeneration after partial degradation is under the control of pulp progenitors. A series of questions arise from recent researches on tissue engineering. In this series of questions, we compare the therapeutic potential of pluripotent embryonic and adult stem cells, both being used in cell-based dental therapies. Crucial questions arise on the origin of stem cells and the localization of niches of progenitors in adult teeth. Circulating progenitor cells may also be candidate for promoting pulp regeneration. Then, we focus on strategies allowing efficient progenitors recruitment. Along this line, we compare the potential of embryonic stem cells versus adult stem cells. Re-programming adult pulp cells to become induced pluripotent stem cells constitute another option. Genes, transcription factors and growth factors may be used to stimulate the differentiation cascade. Extracellular matrix molecules or some bioactive specific domains after enzymatic cleavage may also contribute to the formation of an artificial pulp and ultimately to its mineralization.
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Suchánek, Jakub, Tomáš Soukup, Romana Ivančaková, Jana Karbanová, Věra Hubková, Robert Pytlík, and Lenka Kučerová. "Human Dental Pulp Stem Cells – Isolation and Long Term Cultivation." Acta Medica (Hradec Kralove, Czech Republic) 50, no. 3 (2007): 195–201. http://dx.doi.org/10.14712/18059694.2017.82.
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Human adult mesenchymal stem cells (MSCs) are rare elements living in various organs (e.g. bone marrow, skeletal muscle), with capability to differentiate in various cell types (e.g. chondrocytes, adipocytes and osteoblasts). In the year 2000, Gronthos and co-workers isolated stem cells from the human dental pulp (DPSCs). Later on, stem cells from exfoliated tooth were also obtained. The aims of our study were to establish protocol of DPSCs isolation and to cultivate DPSCs either from adult or exfoliated tooth, and to compare these cells with mesenchymal progenitor cell (MPCs) cultures. MPCs were isolated from the human bone marrow of proximal femur. DPSCs were isolated from deciduous and permanent teeth. Both cell types were cultivated under the same conditions in the media with 2 % of FCS supplemented with PDGF and EGF growth factors. We have cultivated undifferentiated DPSCs for long time, over 60 population doublings in cultivation media designed for bone marrow MPCs. After reaching Hayflick’s limit, they still have normal karyotype. Initial doubling time of our cultures was from 12 to 50 hours for first 40 population doublings, after reaching 50 population doublings, doubling time had increased to 60–90 hours. Regression analysis of uncumulated population doublings proved tight dependence of population doublings on passage number and slow decrease of proliferation potential. In comparison with bone marrow MPCs, DPSCs share similar biological characteristics and stem cell properties. The results of our experiments proved that the DPSCs and MPCs are highly proliferative, clonogenic cells that can be expanded beyond Hayflick’s limit and remain cytogenetically stable. Moreover we have probably isolated two different populations of DPSCs. These DPSCs lines differed one from another in morphology. Because of their high proliferative and differentiation potential, DPSCs can become more attractive, easily accessible source of adult stem cells for therapeutic purposes.
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Luo, Lihua, Yan He, Xiaoyan Wang, Brian Key, Bae Hoon Lee, Huaqiong Li, and Qingsong Ye. "Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair." Stem Cells International 2018 (2018): 1–15. http://dx.doi.org/10.1155/2018/1731289.
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This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.
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About, I. "Dentin Regeneration in vitro." Advances in Dental Research 23, no. 3 (June 15, 2011): 320–24. http://dx.doi.org/10.1177/0022034511405324.
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The elaboration of dentin-pulp engineering strategies requires the investigation of not only progenitor cell potentials but also their interactions with other non-progenitor “supportive” cells. Under severe caries lesions, progenitor cells may be activated by growth factors released after the acidic dissolution of carious dentin. However, dentin regeneration has also been observed after traumatic injuries without any significant dentin dissolution. This raises questions about the origin of signals involved in progenitor cell activation, migration, and differentiation. Study models such as the entire tooth culture and co-cultures of pulp and endothelial cells highlighted the role of interactions between the different pulp cell types and the pivotal role they play in dentin regeneration. Injured pulp fibroblasts secrete growth factors involved in progenitor cell activation and differentiation as well as neoangiogenesis which may pave the pathways for progenitor cell migration. This appears to be the first paper to focus on this very important field in dental pulp biology.
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Kitamura, Chiaki, Tatsuji Nishihara, Masamichi Terashita, Yasuhiko Tabata, Eijiro Jimi, Ayako Washio, and Shizu Hirata. "Regeneration Approaches for Dental Pulp and Periapical Tissues with Growth Factors, Biomaterials, and Laser Irradiation." Polymers 3, no. 4 (October 12, 2011): 1776–93. http://dx.doi.org/10.3390/polym3041776.
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Bae, Sejin, Bueonguk Kang, Hyungbin Lee, Harrison Luu, Eric Mullins, and Karl Kingsley. "Characterization of Dental Pulp Stem Cell Responses to Functional Biomaterials Including Mineralized Trioxide Aggregates." Journal of Functional Biomaterials 12, no. 1 (February 24, 2021): 15. http://dx.doi.org/10.3390/jfb12010015.
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Introduction: Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo growth, viability, and proliferation, as well as differentiation of DPSC—although much remains to be discovered. Based upon this information, the primary objective of this study was to understand the functional biomaterials needed to more effectively direct DPSC viability, growth, and proliferation. Methods: Using an approved protocol, previously collected and isolated samples of DPSC from an existing repository were used. Previously established stem cell biomarkers (Sox-2, Oct-4, NANOG) from each isolate were correlated with their proliferation rates or doubling times to categorize them into rapid, intermediate, or slow-dividing multipotent DPSC. Growth factors and other functional dental biomaterials were subsequently tested to evaluate DPSC responses in proliferation, viability, and morphology. Results: Differential responses were observed among DPSC isolates to growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic protein (BMP-2), and functional biomaterials such as mineralized trioxide aggregates (MTA). The responsiveness of DPSC isolates did not correlate with any single factor but rather with a combination of proliferation rate and biomarker expression. Conclusions: These data strongly suggest that some, but not all, DPSC isolates are capable of a robust and significant in vitro response to differentiation stimuli, although this response is not universal. Although some biomarkers and phenotypes that distinguish and characterize these DPSC isolates may facilitate the ability to predict growth, viability, and differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses to these functional biomaterials for biotechnology and bioengineering applications.
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Liu, Guolin, Guoquan Xu, Zhenhua Gao, Zhenhai Liu, Junji Xu, Jinsong Wang, Chunmei Zhang, and Songlin Wang. "Demineralized Dentin Matrix Induces Odontoblastic Differentiation of Dental Pulp Stem Cells." Cells Tissues Organs 201, no. 1 (November 17, 2015): 65–76. http://dx.doi.org/10.1159/000440952.
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The aim of this study was to investigate the effect of demineralized dentin matrix (DDM) on dental pulp stem cells (DPSCs) and the potential of complexes with DPSCs and DDM for mineralized tissue formation. Stem cells derived from the dental pulp of healthy pigs aged 18 months were isolated and cultured. DPSCs were incubated with alpha-minimum essential medium treated with DDM extract at 1 mg/ml (DDM1) or 10 mg/ml (DDM10). The concentrations of 3 growth factors in DDM extract was measured by enzyme-linked immunosorbent assay. Adhesion of DPSCs on DDM and hydroxyapatite-tricalcium phosphate (HA-TCP) surfaces was observed using scanning electron microscopy. Cell proliferation was evaluated with cell counting kit-8 and migration by Transwell migration assays. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) and alizarin red staining, ALP activity and real-time polymerase chain reaction analysis of markers of ALP, runt-related transcription factor 2, type I collagen, dentin matrix acidic phosphoprotein-1, osteonectin and dentin sialophosphoprotein (DSPP). Finally, DPSCs were combined with DDM and placed subcutaneously in nude mice for 12 weeks; DPSCs combined with HA-TCP and DDM alone served as controls. DDM could promote DPSC adhesion, migration and odontoblastic differentiation. Mineralized tissue formation was observed with the DPSC and DDM combination and the DPSC and HA-TCP combination. The mineralized tissue of the DPSC + DDM combination stained positive for DSPP, similar to the dentin tissue. These results indicate that DDM induces DPSC odontoblastic differentiation, suggesting applications for dentin regeneration.
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Olatz, Crende, García-Gallastegui Patricia, Luzuriaga Jon, Badiola Iker, de la Hoz Carmen, Unda Fernando, Ibarretxe Gaskon, and Pineda Jose Ramon. "Is There Such a Thing as a Genuine Cancer Stem Cell Marker? Perspectives from the Gut, the Brain and the Dental Pulp." Biology 9, no. 12 (November 27, 2020): 426. http://dx.doi.org/10.3390/biology9120426.
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The conversion of healthy stem cells into cancer stem cells (CSCs) is believed to underlie tumor relapse after surgical removal and fuel tumor growth and invasiveness. CSCs often arise from the malignant transformation of resident multipotent stem cells, which are present in most human tissues. Some organs, such as the gut and the brain, can give rise to very aggressive types of cancers, contrary to the dental pulp, which is a tissue with a very remarkable resistance to oncogenesis. In this review, we focus on the similarities and differences between gut, brain and dental pulp stem cells and their related CSCs, placing a particular emphasis on both their shared and distinctive cell markers, including the expression of pluripotency core factors. We discuss some of their similarities and differences with regard to oncogenic signaling, telomerase activity and their intrinsic propensity to degenerate to CSCs. We also explore the characteristics of the events and mutations leading to malignant transformation in each case. Importantly, healthy dental pulp stem cells (DPSCs) share a great deal of features with many of the so far reported CSC phenotypes found in malignant neoplasms. However, there exist literally no reports about the contribution of DPSCs to malignant tumors. This raises the question about the particularities of the dental pulp and what specific barriers to malignancy might be present in the case of this tissue. These notable differences warrant further research to decipher the singular properties of DPSCs that make them resistant to transformation, and to unravel new therapeutic targets to treat deadly tumors.
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Ratajczak, Jessica, Annelies Bronckaers, Yörg Dillen, Pascal Gervois, Tim Vangansewinkel, Ronald B. Driesen, Esther Wolfs, Ivo Lambrichts, and Petra Hilkens. "The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering." Stem Cells International 2016 (2016): 1–17. http://dx.doi.org/10.1155/2016/9762871.
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Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.
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Furey, Alyssa, Julie Hjelmhaug, and Doug Lobner. "Toxicity of Flow Line, Durafill VS, and Dycal to Dental Pulp Cells: Effects of Growth Factors." Journal of Endodontics 36, no. 7 (July 2010): 1149–53. http://dx.doi.org/10.1016/j.joen.2010.03.013.
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Suchánek, Jakub, Tereza Suchánková Kleplová, Martin Kapitán, and Tomáš Soukup. "THE EFFECT OF FETAL CALF SERUM ON HUMAN DENTAL PULP STEM CELLS." Acta Medica (Hradec Kralove, Czech Republic) 56, no. 4 (2013): 142–49. http://dx.doi.org/10.14712/18059694.2014.9.
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Aims: Authors studied potential side effects of fetal calf serum (FCS) in cultivation media on human dental pulp stem cells (DPSC) during long term cultivation. Methods: Two lines of DPSC obtained healthy donors (male 22 years, female 23 years) were used. Both lines were cultivated under standard cultivation conditions in four different media containing 10% or 2% FCS and substituted with growth factors. During long term cultivation proliferation ability, karyotype and phenotype of DPSC were measured. Results: Both lines of DPSC cultivated in a media containing 2% FCS and ITS supplement showed the highest number of population doublings. On the other hand the proliferation rate of DPSC cultivated in a media with 2% FCS without ITS supplement was slowest. Proliferation rate of DPSC cultivated in 10% FCS media with or without FGF-2 was comparable. DPSC cultivated in a media with 10% FCS showed a significantly higher amount of chromosomal aberrations. These chromosomal aberrations do not seem to be clonal but surprisingly we found large amounts of tetraploid cells in the 9th passage in both media containing 10% FCS. Conclusions: Our study proved that cultivation of DPSC in media containing higher concentration of FCS has critical side effects on cell chromosomal stability.