DPSCs and SHED in Tissue Engineering and Regenerative Medicine

Recently, dental stem and progenitor cells have been harvested from periodontal tissues such as dental pulp, periodontal ligament, follicle, and papilla. These cells have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and multilineage differentiation capacity. These dental stem and progenitor cells are known to be derived from ectomesenchymal origin formed during tooth development. A great deal of research has been accomplished for directing osteoblastic/cementoblastic differentiation and neural differentiation from dental stem cells. To differentiate dental stem cells for use in tissue engineering and regenerative medicine, there needs to be efficient in vitro differentiation toward the osteoblastic/cementoblastic and neural lineage with well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source. This review focuses on the multilineage differentiation capacity, especially into osteoblastic/cementoblastic lineage and neural lineages, of dental stem cells such as dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), periodontal ligament stem cells (PDLSC), and dental papilla stem cells (DPPSC). It also covers various experimental strategies that could be used to direct lineage-specific differentiation, and their potential applications in tissue engineering and regenerative medicine.

Since the disclosure of adult mesenchymal stem cells (MSCs), there have been an intense investigation on the characteristics of these cells and their potentialities. Dental stem cells (DSCs) are MSC-like populations with self-renewal capacity and multidifferentiation potential. Currently, there are five main DSCs, dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs) and dental follicle precursor cells (DFPCs). These cells are extremely accessible, prevail during all life and own an amazing multipotency. In the past decade, DPSCs and SHED have been thoroughly studied in regenerative medicine and tissue engineering as autologous stem cells therapies and have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and auto-immune conditions, in both animal and human models, and most recently some of them in human clinical trials. In this review, we focus the characteristics, the multiple roles of DSCs and its potential translation to clinical settings. These new insights of the apparently regenerative aptitude of these DSCs seems quite promising to investigate these cells abilities in a wide variety of pathologies.Key messagesDental stem cells (DSCs) have a remarkable self-renewal capacity and multidifferentiation potential;DSCs are extremely accessible and prevail during all life;DSCs, as stem cells therapies, have shown amazing therapeutic abilities in oro-facial, neurologic, corneal, cardiovascular, hepatic, diabetic, renal, muscular dystrophy and autoimmune conditions;DSCs are becoming extremely relevant in tissue engineering and regenerative medicine.

Stem cells play a crucial role in the physiology of dental tissues. Today six different types of stem cells/progenitor cells have been isolated and characterized from dental tissues: dental pulp stem cells (DPSCs), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), stem cells from exfoliated deciduous teeth (SHED), dental follicle stem cells (DFPCs), and periapical cyst mesenchymal stem cells (hPCy-MSCs). These dental stem cells (DSCs) are undifferentiated mesenchymal stem cells characterized by their self-renewal capacity and the ability to differentiate in osteoblasts, adipocytes, and chondrocytes. The dental tissue-derived stem cells physiologically possess potent capacities to differentiate into odontogenic cells; however, their exceptional regenerative ability can be applied not only in dentistry but also in different fields of regenerative medicine such as bone regeneration. Although they are all derived from dental tissues, the properties of these DSC populations such as differentiation potential and expression of specific markers are minimally different according to the site from which they are isolated. These mesenchymal stem cells participate also in the regeneration of nontooth tissues, such as nerve, muscle, bone, liver, and pancreas. Consequently, these DSCs have been used for tissue engineering studies in large animal models to assess their potential in preclinical applications. The MSCs contained within dental tissues are easily accessible stem cells and the isolation of MSCs from these sources may still be convenient because it requires easy surgical methods with lack of morbidity at the donor site. In this regard, DSCs may represent a good cell source that could be a benefit in cellular therapy for several regenerative medicine applications. In this chapter, we will summarize research findings regarding the area of dental stem cell biology applied to regenerative medicine and dentistry in light of potential clinical applications of these cells in future.

Recent advances in tissue engineering and regenerative medicine offer a long-term solution through biological repair, replacement of damaged teeth or maintenance and improvement of tissue and organ function through the use of stem cells. Stem cells or also called universal cells, progenitor cells or precursor cells; they are primitive, undifferentiated, clonogenic cells that are characterized by their self-renewal capabilities and that can be differentiated into more specialized cells with specific functions. Currently many sources are known from where you can obtain stem cells, one of which are those obtained from oral or dental tissues, called dental stem cells (DSC), from where it has been possible to identify, isolate and characterize around 8 unique populations: dental pulp stem cells (DPSC), human exfoliated deciduous tooth stem cells (SHED), periodontal ligament stem cells (PLDSC), dental follicle stem cells (DFSC), stem cells derived from bone alveolar (CMHA), the stem cells of the apical papilla (SCAP), the stem cells of the dental germ (DGSC) and the gingival stem cells (GSC). These DSC have attracted attention in recent years due to their accessibility, plasticity and high proliferation capacity. Currently, DSC have shown that they can be used in endodontic and periodontal regenerative therapy, in the regeneration of dentin and bone and in dental bioengineering. Tissue engineering methodologies combined with a greater understanding of the biology of DSCs will provide powerful tools for a broader spectrum of their application in various future therapeutic strategies.

To the Editor: The molecular mechanisms and the control of smooth muscle cell (SMC) differentiation have been extensively investigated because of its therapeutic potential.1 To date, different cell types have been used to study SMC differentiation, including a variety of mouse embryonic stem cells,2 adult stem cells,3,4 and others.5 Because several fundamental differences exist between mouse and human embryonic development,6 lack of a good model system to study human SMC differentiation has hampered the progress of translating SMC knowledge to novel clinical therapies. Human embryonic stem (hES) cells provide a valuable source of cells for studying human cell differentiation and developing therapeutic potentials in regenerative medicine. Since the initial report describing the derivation of hES cells,7 a variety of studies have established in vitro differentiation strategies to several lineages. Recently, it has been demonstrated that vascular progenitors derived from hES cells could be differentiated into endothelial cells and SMCs by endothelial …

Over the past decade there has been a dramatic progress in the field of stem cell research and a rapid surge in investigation of stem cell therapies. Current clinical trials using a variety of stem cell types are addressing a wide spectrum of conditions. Among different types of adult stem cells discovered, dental stem cells are among the newest found in the MSC repertoire. Dental stem cells can be isolated relatively easily through minimally invasive procedures from both young and adult populations. In particular, dental pulp stem cells (DPSCs) are found to have outstanding potentials because of their superior proliferation, multi-potent differentiation, regeneration, immunoprivileged, and immunomodulatory properties. In addition, DPSCs can be reprogrammed into induced pluripotent stem cells (iPSCs) with high efficiency, possibly due to their dual meso-ectodermal origin and intrinsic expression of pluripotent factors. The current chapter discusses their origin, biological niche, functional properties, reprogramming capability, and application potentials for therapeutics, cell banking, and tissue engineering toward construction of both dental and non-dental tissues. This chapter consists of three main sections: (1) Developmental biology and organization of dental-related stem cells; (2) Dental stem cell properties for cell-based therapeutics; (3) Potentials of dental stem cells for tissue engineering and cell banking. Overall this review provides current biological knowledge on dental stem cells and their translational applications at both in vitro and in vivo levels. The chapter is designed for both clinicians and researchers involved in odontogenesis and stem cell research alike.

Characterization of the Cellular Responses of Dental Mesenchymal Stem Cells to the Immune System

British Society for Gene and Cell Therapy (BSGCT) Conference AbstractsRoyal HollowayUniversity of London17–19 April, 2013

Regenerative medicine has garnered significant attention due to its transformative impact on disease management and the restoration of optimal bodily functions. Stem cells, a cornerstone of regenerative medicine, are particularly renowned for their remarkable capacity to facilitate tissue regeneration and repair, revolutionizing modern healthcare by offering diverse treatment avenues for multiple conditions. Dental pulp stem cells (DPSCs), a subset of postnatal stem cells, are especially noteworthy for their extensive proliferation and ability to differentiate into various specialized cell types. In the realm of pediatric dentistry, there exists a pressing need for advancements in regenerative medicine. Thorough research in this domain has the potential to propel evidence-based pediatric dentistry, ensuring that children receive tailored, high-quality care. Stem cells hold immense promise in pediatric dentistry by offering less invasive and regenerative solutions for a range of childhood dental issues and congenital anomalies. This research, initiated on 04 October 2023, was instigated following an exhaustive review of existing literature utilizing databases like PubMed, Web of Science, and Cochrane. The literature search encompassed a wide array of medical terminologies. Dental stem cells are categorized into four major types: DPSCs, stem cells from human exfoliated deciduous teeth (SHED), stem cells of the apical papilla (SCAP), and periodontal ligament stem cells (PDLSCs). Pediatric dentistry, encompassing endodontics, orthodontics, periodontics, and the treatment of craniofacial defects, stands to benefit significantly from the potential of dental stem cells. The preservation of dental pulp stem cells extracted from deciduous and permanent teeth through tooth banking offers a source for future regenerative therapies. The preservation process involves multiple comprehensive steps. In summary, dental stem cells present a promising avenue within pediatric dentistry, offering multifaceted applications ranging from pulpal regeneration and dentin repair to orthodontic support and the treatment of craniofacial anomalies.

Recent studies indicate that cardiac transfer of adult stem cells can have a favorable impact on tissue perfusion and contractile performance of the infarcted heart. Several cell sources are being explored in an effort to regenerate infarcted myocardium, including hematopoietic stem cells, endothelial progenitor cells, cardiac resident stem cells, bone marrow–derived multipotent stem cells, and mesenchymal stem cells (MSCs). Each of these cell types may have its own profile of advantages, limitations, and practicability issues in specific settings. Studies comparing the regenerative capacity of distinct cell populations are scarce. Most clinical investigators have therefore chosen a pragmatic approach by using unselected bone marrow cells that contain different stem cell populations. Basic scientists, by contrast, are focusing more on specific cell populations in a quest to understand the biological foundations of cell therapy and to identify the most promising stem cells for cardiac regeneration.1 See p 214 MSCs are a rare population of self-renewing, multipotent cells present in adult bone marrow. Although MSCs represent <0.01% of all nucleated bone marrow cells, they can be readily expanded in vitro. In defined culture media, MSCs differentiate into several mesenchymal cell lineages, including cardiomyocytes.2,3 When injected into normal adult myocardium, MSCs differentiate into cardiomyocyte-like cells with sarcomeric organization.4 In an earlier study in pigs with myocardial infarction (MI), MSCs grafted into the infarcted area were shown to express muscle-specific markers and to improve regional wall motion.5 Ease of isolation, high expansion capability, and cardiomyogenic potential have led to the proposition that MSCs may be a good choice for cell-based therapies of MI.6 In a report published in this issue of Circulation , Dai et al7 have …

Dental stem cells (DSCs), a distinct subset of mesenchymal stem cells (MSCs), are isolated from dental tissues, such as dental pulp, exfoliated deciduous teeth, periodontal ligament, and apical papilla. They have emerged as a promising source of stem cell therapy for tissue regeneration and autoimmune disorders. The main types of DSCs include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Each type exhibits distinct advantages: easy access via minimally invasive procedures, multi-lineage differentiation potential, and excellent ethical acceptability. DSCs have demonstrated outstanding clinical efficacy in oral and maxillofacial regeneration, and their long-term safety has been verified. In oral tissue regeneration, DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair. A defining advantage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration, which render them a better option for oral tissue regenerative therapies. Beyond oral applications, DSCs also exhibit promising potential in the treatment of systemic diseases, including type Ⅱ diabetes and autoimmune diseases due to their immunomodulatory effects. Moreover, extracellular vesicles (EVs) derived from DSCs act as critical mediators for DSCs' paracrine functions. Possessing regulatory properties similar to their parental cells, EVs are extensively utilized in research targeting tissue repair, immunomodulation, and regenerative therapy-offering a "cell-free" strategy to mitigate the limitations associated with cell-based therapies. Despite these advancements, standardizing large-scale manufacturing, maintaining strict quality control, and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use. Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy. In conclusion, DSCs and their EVs represent a transformative approach in regenerative medicine, and increasing clinical evidence supports their application in oral and systemic diseases. Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.

Introduction: Stem cells (SCs), known as cells with characteristics such as self-renewal and multilineage differentiation, are generally obtained from two sources: Embryonic stem cells (ESCs) and adult stem cells (ASCs). SC research is expected to play a pivotal role in future medicine. The aim of the present review was to introduce dental and nondental SCs, examining the general characteristics, in vivo and in vitro differentiation capacities, immunosuppressive properties as well as the application of SCs in dentistry and regenerative medicine. Methods: In October 2015, PubMed, Scopus were searched by experienced researchers with the query "stem cells and dentistry "and a focus on SC and dental journals. Results: In the field of dentistry, ASCs, isolated from different structures, are divided into different subpopulations: Dental SCs, population of SCs isolated from different components of immature and mature teeth and nondental SCs, and those isolated from oromaxillofacial tissues. Conclusions: It appears that dental and nondental SCs are popular resources of SCs because of easier accessibility and fewer ethical problems. In addition, they have a high differentiation capacity into different cell lineages. Different studies have introduced dental and nondental SCs as suitable SC sources for SC therapy in dentistry and regenerative medicine.

Miniature pigs have been considered as a recommended large animal model for biomedical research. Mesenchymal stem cells offer promising potential for tissue regeneration. Recent studies have suggested that dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) may provide more reliable strategies for the treatment of dental diseases using a cell-based tissue engineering approach. The aim of this study was to isolate and compare the characteristics of the DPSCs and PDLSCs of a miniature pig breed to the DPSCs and PDLSCs of a domestic farm pig breed. Stem cells of the DP and PDL were obtained from a male Yucatan miniature pig (nine months old) and a male domestic farm pig breed (six months old). The cell morphology, surface stem cell marker expression, proliferation, and osteogenic differentiation ability were evaluated. Under a light microscope, the DPSCs and PDLSCs of the miniature pig breed had morphologies similar to those of the domestic farm pig breed. The proliferation of PDLSCs in both animals showed no significant differences, except on day five, whereas the proliferation of DPSCs was significantly higher in the miniature pig breed. However, the osteogenic abilities of the DPSCs and PDLSCs from the miniature pig breed were significantly lower compared to the domestic farm pig breed. This observation emphasizes the need for the breed-specific optimization of an osteogenic differentiation culture protocol for Yucatan miniature pig DPSCs and PDLSCs before application to cell-based therapy for tissue engineering and regenerative medicine.

PERIODONTAL LIGAMENT STEM CELL TRANSPLANTATION PROMISING, STUDY FINDS

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