Dental pulp stem cells, niches, and notch signaling in tooth injury

Stem cells guarantee tissue repair and regeneration throughout life. The decision between cell self-renewal and differentiation is influenced by a specialized microenvironment called the 'stem cell niche'. In the tooth, stem cell niches are formed at specific anatomic locations of the dental pulp. The microenvironment of these niches regulates how dental pulp stem cell populations participate in tissue maintenance, repair, and regeneration. Signaling molecules such as Notch proteins are important regulators of stem cell function, with various capacities to induce proliferation or differentiation. Dental injuries often lead to odontoblast apoptosis, which triggers activation of dental pulp stem cells followed by their proliferation, migration, and differentiation into odontoblast-like cells, which elaborate a reparative dentin. Better knowledge of the regulation of dental pulp stem cells within their niches in pathological conditions will aid in the development of novel treatments for dental tissue repair and regeneration.     

Application of neurotransmitters and dental stem cells for pulp regeneration: A review

IntroductionAlthough there have been many studies on stem cells, few have investigated how neurotransmitters and stem cell proliferation interact to regenerate dental pulp. Dental pulp regeneration is an innovative procedure for reviving dental pulp, if feasible for the entire tooth. Upon tooth injury, activated platelets release serotonin and dopamine in bulk to mobilize dental pulp stem cells to mediate natural dental repair. This has induced research on the role of neurotransmitters in increasing the proliferation rate of stem cells. This review also covers prospective future treatments for dental pulp regeneration.MethodsA literature search was performed via PubMed and ScienceDirect from 2001 to 2022, using the keywords “neurotransmitter,” “stem cell,” “tooth regeneration,” “tooth repair,” “regenerative dentistry,” and “dental pulp.” Different inclusion/exclusion criteria were used, and the search was restricted to English articles.ResultsNine publications reporting neurotransmitter interactions with stem cells for tooth and pulp regeneration were selected.ConclusionNeurotransmitters were found to interact with dental stem cells. Evidence pointing to neurotransmitters as a factor in the increased proliferation of stem cells was found. This review thus gives hope for tooth pulp regeneration and repair.     

Mesenchymal stem cells in the dental tissues: perspectives for tissue regeneration

In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration. This review describes new findings in the field of dental stem cell research and on their potential use in the tissue regeneration.     

牙源性干细胞及牙髓再生的研究进展

牙髓组织中含有细胞、血管、神经和纤维等,是一个复杂的3D结构系统。随着干细胞生物学和组织工程学的相互结合和促进,牙髓再生逐渐成为可能。牙体组织中分离出的多种干细胞,如牙髓干细胞、脱落乳牙牙髓干细胞、根尖牙乳头干细胞、牙囊干细胞等,都具有再生牙髓的潜能。文章就牙源性干细胞及以牙源性干细胞为基础的牙髓再生的研究进展做一综述。     

Somatic stem cells for regenerative dentistry

Complex human tissues harbour stem cells and/or precursor cells, which are responsible for tissue development or repair. Recently, dental tissues such as periodontal ligament (PDL), dental papilla or dental follicle have been identified as easily accessible sources of undifferentiated cells. The dental stem cell biology might provide meaningful insights into the development of dental tissues and cellular differentiation processes. Dental stem cells could also be feasible tools for dental tissue engineering. Constructing complex structures like a periodontium, which provides the functional connection between a tooth or an implant and the surrounding jaw, could effectively improve modern dentistry. Dental precursor cells are attractive for novel approaches to treat diseases like periodontitis, dental caries or to improve dental pulp healing and the regeneration of craniofacial bone and teeth. These cells are easily accessible and, in contrast to bone-marrow-derived mesenchymal stem cells, are more closely related to dental tissues. This review gives a short overview of stem cells of dental origin.     

根尖牙乳头干细胞的研究现状

根尖周牙乳头干细胞(Stem Cells from the Apical Papilla,SCAP)存在于未完全发育成形的恒牙根尖周组织中,是具有高度增生、自我更新能力和多向分化潜能的成体干细胞。SCAP是牙根发育时成牙本质细胞的重要来源,在牙根的形成和发育中起着重要的作用,SCAP的研究将对牙髓修复,牙本质再生以及生物学牙根组织工程产生重要作用。该文就其研究现状作一综述。     

Dental pulp stem cells in regenerative dentistry

Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer’s disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.     

Stem cells and the dental pulp: potential roles in dentine regeneration and repair

The dentine-pulp complex displays exquisite regenerative potential in response to injury. The postnatal dental pulp contains a variety of potential progenitor/stem cells, which may participate in dental regeneration. A population of multipotent mesenchymal progenitor cells known as dental pulp stem cells with high proliferative potential for self-renewal has been described and may be important to the regenerative capacity of the tissue. The nature of the progenitor/stem cell populations in the pulp is of importance in understanding their potentialities and development of isolation or recruitment strategies, and allowing exploitation of their use in regeneration and tissue engineering. Various strategies will be required to ensure not only effective isolation of these cells, but also controlled signalling of their differentiation and regulation of secretory behaviour. Characterization of these cells and determination of their potentialities in terms of specificity of regenerative response will form the foundation for development of new clinical treatment modalities, whether involving directed recruitment of the cells and seeding of stem cells at sites of injury for regeneration or use of the stem cells with appropriate scaffolds for tissue engineering solutions. Such approaches will provide an innovative and novel biologically based new generation of clinical treatments for dental disease.     

Clinical utility of stem cells for periodontal regeneration

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We considered and described the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.     

Dental stem cells and their potential role in apexogenesis and apexification

Injury to an immature permanent tooth may result in cessation of dentine deposition and root maturation leaving an open root apex and thin dentinal walls that are prone to fracture. Endodontic treatment is often complicated and protracted with an uncertain prognosis frequently resulting in premature tooth loss. Postnatal stem cells, which are capable of self‐renewal, proliferation and differentiation into multiple specialized cell lineages have been isolated and identified within the dental pulp, apical papilla and periodontal ligament. The ability of these cells to produce pulp‐dentine and cementum‐periodontal ligament complexes in vivo suggest potential applications involving stem cells, growth factors and scaffolds for apexification or apexogenesis. Similar protein expression amongst dental stem cells possibly implicates a common origin; however, the dominant cells to repopulate an open apex will be directed by local environmental cues. A greater understanding of the structure and function of cells within their environment is necessary to regulate and facilitate cellular differentiation along a certain developmental path with subsequent tissue regeneration. This review focuses on development of the apical tissues, dental stem cells and their possible involvement clinically in closing the open root apex. MEDLINE and EMBASE computer databases were searched up to January 2009. Abstracts of all potentially relevant articles were scanned and their contents identified before retrieval of full articles. A manual search of article reference lists as well as a forward search on selected authors of these articles was undertaken. It appears that dental stem cells have the potential for continued cell division and regeneration to replace dental tissues lost through trauma or disease. Clinical applications using these cells for apexogenesis and apexification will be dependent on a greater understanding of the environment at the immature root end and what stimulates dental stem cells to begin dividing and then express a certain phenotype.     

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??With the discovery of dental stem cells and the development of tissue engineering??tissue engineering technology based on stem cells provides a new direction and strategy for the treatment of dental pulp disease. In this article??we review the current studies of dental stem cells??including dental pulp stem cells??apical papilla stem cells and stem cells from exfoliated deciduous teeth??in pulp-dentin regeneration. The use of stem cell sheets and exosomes derived from dental stem cells are discussed as well.     

牙本质基质在组织再生中的应用

组织器官病变严重影响到人们的生活质量,组织器官缺损可能威胁人们的生命,组织、器官缺损的修复和功能重建是现代医学面临的挑战。组织工程为再生组织器官带来希望。组织工程支架为细胞的生长、增殖和分化提供了微环境,而且影响着形成组织的大小和形态。牙本质基质作为一种天然的生物活性支架,具有良好的生物相容性,在组织工程中得到广泛的应用,成为研究热点。学者们以牙本质基质为支架,开展了包括牙根、牙周、牙髓、骨等软硬组织缺损修复的研究,取得了一系列重要进展。本文对牙本质生物学特性、牙本质基质在组织再生中的应用等进行综述,为临床应用牙本质基质进行组织再生提供参考。     

生长因子对牙髓干细胞的矿化作用

健康牙髓中含有的具有多向分化、高效增殖和自我更新潜能的牙髓干细胞,在牙髓损伤后牙本质修复再生和牙/骨组织工程中具有至关重要的作用.本文就牙髓干细胞的矿化潜能、生长因子及其在促牙髓干细胞矿化和作用机制方面的研究进展作一综述.     

Dental follicle stem cells and tissue engineering

Adult stem cells are multipotent and can be induced experimentally to differentiate into various cell lineages. Such cells are therefore a key part of achieving the promise of tissue regeneration. The most studied stem cells are those of the hematopoietic and mesenchymal lineages. Recently, mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, and dental follicle. The dental follicle is a loose connective tissue that surrounds the developing tooth. Dental follicle stem cells could therefore be a cell source for mesenchymal stem cells. Indeed, dental follicle is present in impacted teeth, which are commonly extracted and disposed of as medical waste in dental practice. Dental follicle stem cells can be isolated and grown under defined tissue culture conditions, and recent characterization of these stem cells has increased their potential for use in tissue engineering applications, including periodontal and bone regeneration. This review describes current knowledge and recent developments in dental follicle stem cells and their application.     

牙髓再生的研究进展

活髓对于维持牙齿内稳态十分重要。理想的牙髓治疗方法应包括再生性牙髓治疗,即坏死或活力减退的牙髓被活髓所代替,最终牙齿活力恢复。随着组织工程的发展,牙髓再生成为可能,本文将从干细胞、支架、生长因子3个方面对牙髓再生相关的问题做一综述。     

Adipose-derived stem cells in dentistry

In the last decade, applications of tissue engineering technology in dental regenerative medicine have expanded enormously. In particular, the use of mesenchymal stem cells, which are highly proliferative and have the capacity to differentiate into osteogenic, chondrogenic, and adipogenic cells, promises to have a positive impact on the future of dentistry. The therapeutic potential of human multipotent mesenchymal stem cells, which are harvested from bone marrow and adipose tissue, has generated a markedly increased interest within a wide range of biomedical disciplines. Adipose-derived stem cells are especially interesting because of their strong potential for cell differentiation and growth factor secretion. Furthermore, these cells have some advantages over stem cells from other sources, including the fact that a large number of stem cells can be easily and quickly isolated from subcutaneous adipose tissue.In clinical dental therapy, several non-stem-cell-based methods have been developed for periodontal and bone tissue engineering. These methods include the stimulation of regeneration using enamel matrix proteins, guided tissue regeneration, various bone grafting techniques, and the application of growth factors and have been applied either alone or in combination. However, there are various limitations and shortcomings in the currently available methods. Therefore, it will be a significant step forward to establish dental tissue engineering techniques using mesenchymal stem cells. In this review, the fundamentals of periodontal tissue regeneration and bone tissue engineering are discussed. In particular, the use of adipose-derived stem cells in periodontal tissue regeneration, bone tissue engineering, and the engineering of other complex tissues are discussed.     

Dental pulp regeneration via cell homing

The typical treatment for irreversibly inflamed/necrotic pulp tissue is root canal treatment. As an alternative approach, regenerative endodontics aims to regenerate dental pulp‐like tissues using two possible strategies: cell transplantation and cell homing. The former requires exogenously transplanted stem cells, complex procedures and high costs; the latter employs the host's endogenous cells to achieve tissue repair/regeneration, which is more clinically translatable. This systematic review examines cell homing for dental pulp regeneration, selecting articles on in vitro experiments, in vivo ectopic transplantation models and in situ pulp revascularization. MEDLINE/PubMed and Scopus databases were electronically searched for articles without limits in publication date. Two reviewers independently screened and included papers according to the predefined selection criteria. The electronic searches identified 46 studies. After title, abstract and full‐text examination, 10 articles met the inclusion criteria. In vitro data highlighted that multiple cytokines have the capacity to induce migration, proliferation and differentiation of dental pulp stem/progenitor cells. The majority of the in vivo studies obtained regenerated connective pulp‐like tissues with neovascularization. In some cases, the samples showed new innervation and new dentine deposition. The in situ pulp revascularization regenerated intracanal pulp‐like tissues with neovascularization, innervation and dentine formation. Cell homing strategies for pulp regeneration need further understanding and improvement if they are to become a reliable and effective approach in endodontics. Nevertheless, cell homing currently represents the most clinically viable pathway for dental pulp regeneration.     

Regenerative endodontics in light of the stem cell paradigm

Stem cells play a critical role in development and in tissue regeneration. The dental pulp contains a small sub-population of stem cells that are involved in the response of the pulp to caries progression. Specifically, stem cells replace odontoblasts that have undergone cell death as a consequence of the cariogenic challenge. Stem cells also secrete factors that have the potential to enhance pulp vascularisation and provide the oxygen and nutrients required for the dentinogenic response that is typically observed in teeth with deep caries. However, the same angiogenic factors that are required for dentine regeneration may ultimately contribute to the demise of the pulp by enhancing vascular permeability and interstitial pressure. Recent studies focused on the biology of dental pulp stem cells revealed that the multipotency and angiogenic capacity of these cells could be exploited therapeutically in dental pulp tissue engineering. Collectively, these findings suggest new treatment paradigms in the field of endodontics. The goal of this review is to discuss the potential impact of dental pulp stem cells to regenerative endodontics.     

细胞外基质支架及其在牙髓再生中应用的研究进展

实现全牙髓功能性再生是牙髓及根尖周疾病治疗的理想目标。以干细胞为基础的再生医学技术为牙髓再生带来了新的希望,而支架材料在其中发挥重要作用。通过化学、物理或生物学等方法去除组织、器官中的细胞及抗原,可获得天然脱细胞的细胞外基质支架。其具有良好的物理特性、生物相容性以及生物降解性,能够促进干细胞黏附、生长、增殖及分化,同时具有低免疫原性,避免过敏反应和疾病传播,被认为是再生医学一种新型的生物支架。文章就细胞外基质支架的制备、特性及其在牙髓再生中应用的研究进展做一综述。