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Cell Reports Dec 2022Mammalian teeth develop from the inductive epithelial-mesenchymal interaction, an important mechanism shared by many organs. The cellular basis for such interaction...
Mammalian teeth develop from the inductive epithelial-mesenchymal interaction, an important mechanism shared by many organs. The cellular basis for such interaction remains elusive. Here, we generate a dual-fluorescence model to track and analyze dental cells from embryonic to postnatal stages, in which Pitx2 epithelium and Msx1 mesenchyme are sufficient for tooth reconstitution. Single-cell RNA sequencing and spatial mapping further revealed critical cellular dynamics during molar development, where tooth germs are organized by Msx1Sdc1 dental papilla and surrounding dental niche. Surprisingly, niche cells are more efficient in tooth reconstitution and can directly regenerate papilla cells through interaction with dental epithelium. Finally, from the dental niche, we identify a group of previously unappreciated migratory Msx1 Sox9 cells as the potential cell origin for dental papilla. Our results indicate that the dental niche cells directly contribute to tooth organogenesis and provide critical insights into the essential cell composition for tooth engineering.
Topics: Tooth
PubMed: 36476878
DOI: 10.1016/j.celrep.2022.111737 -
Clinical Oral Investigations Feb 2022Minimally invasive flap designs have been introduced to enhance blood clot stability and support wound healing. Limited data appear to suggest, that in intrabony... (Randomized Controlled Trial)
Randomized Controlled Trial
The role of surgical flap design (minimally invasive flap vs. extended flap with papilla preservation) on the healing of intrabony defects treated with an enamel matrix derivative: a 12-month two-center randomized controlled clinical trial.
OBJECTIVES
Minimally invasive flap designs have been introduced to enhance blood clot stability and support wound healing. Limited data appear to suggest, that in intrabony defects, better clinical outcomes can be achieved by means of minimally invasive flap compared to more extended flaps. The aim of this study was to evaluate the healing of intrabony defects treated with either minimally invasive surgical flaps or with modified or simplified papilla preservation techniques in conjunction with the application of an enamel matrix derivative (EMD).
MATERIALS AND METHODS
Forty-seven subjects were randomly assigned to either test (N = 23) or control (N = 24) procedures. In the test group, the intrabony defects were accessed by means of either minimally invasive surgical technique (MIST) or modified minimally invasive surgical technique (M-MIST) according to the defect localization while the defects in the control group were treated with either the modified or simplified papilla preservation (MPP) or the simplified papilla preservation technique (SPP). EMD was used as regenerative material in all defects. The following clinical parameters were recorded at baseline and after 12 months: full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), probing depths (PD), clinical attachment level (CAL), and gingival recession (GR). Early healing index (EHI) score was assessed in both groups 1 week following the surgery. CAL gain was set as primary outcome.
RESULTS
After 12 months follow-up, the CAL gain was 4.09 ± 1.68 mm in test group and 3.79 ± 1.67 mm in control group, while the PD reduction was 4.52 ± 1.34 mm and 4.04 ± 1.62 mm for test and control sites. In both groups, a minimal GR increase (0.35 ± 1.11 mm and 0.25 ± 1.03 mm) was noted. No residual PDs ≥ 6 mm were recorded in both groups. CAL gains of 4-5 mm were achieved in 30.4% and in 29.2% of test and control group, respectively. Moreover, CAL gains ≥ 6 mm were recorded in 21.7% of experimental sites and in 20.8% of control sites. No statistically significant differences in any of the evaluated parameters were found between the test and control procedures (P > 0.05). After 1 week post-surgery, a statistically significant difference (P < 0.05) between the groups was found in terms of EHI score.
CONCLUSIONS
Within the limits of this pilot RCT, the results have failed to show any differences in the measured parameters following treatment of intrabony defects with EMD, irrespective of the employed surgical technique.
CLINICAL RELEVANCE
In intrabony defects, the application of EMD in conjunction with either MIST/M-MIST or M-PPT/SPPT resulted in substantial clinical improvements.
Topics: Alveolar Bone Loss; Dental Enamel Proteins; Follow-Up Studies; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Surgical Flaps; Treatment Outcome; Wound Healing
PubMed: 34491446
DOI: 10.1007/s00784-021-04155-5 -
Stem Cell Research & Therapy Sep 2022Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental... (Review)
Review
Dental follicles are necessary for tooth eruption, surround the enamel organ and dental papilla, and regulate both the formation and resorption of alveolar bone. Dental follicle progenitor cells (DFPCs), which are stem cells found in dental follicles, differentiate into different kinds of cells that are necessary for tooth formation and eruption. Runt-related transcription factor 2 (Runx2) is a transcription factor that is essential for osteoblasts and osteoclasts differentiation, as well as bone remodeling. Mutation of Runx2 causing cleidocranial dysplasia negatively affects osteogenesis and the osteoclastic ability of dental follicles, resulting in tooth eruption difficulties. Among a variety of cells and molecules, Nel-like molecule type 1 (Nell-1) plays an important role in neural crest-derived tissues and is strongly expressed in dental follicles. Nell-1 was originally identified in pathologically fused and fusing sutures of patients with unilateral coronal synostosis, and it plays indispensable roles in bone remodeling, including roles in osteoblast differentiation, bone formation and regeneration, craniofacial skeleton development, and the differentiation of many kinds of stem cells. Runx2 was proven to directly target the Nell-1 gene and regulate its expression. These studies suggested that Runx2/Nell-1 axis may play an important role in the process of tooth eruption by affecting DFPCs. Studies on short and long regulatory noncoding RNAs have revealed the complexity of RNA-mediated regulation of gene expression at the posttranscriptional level. This ceRNA network participates in the regulation of Runx2 and Nell-1 gene expression in a complex way. However, non-study indicated the potential connection between Runx2 and Nell-1, and further researches are still needed.
Topics: Bone Remodeling; Calcium-Binding Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Sac; Humans; Osteogenesis; RNA; Stem Cells; Tooth Eruption; Transcription Factors
PubMed: 36175952
DOI: 10.1186/s13287-022-03140-3 -
Journal of Tissue Engineering 2017Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem... (Review)
Review
Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies. The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart. The concept of developing tooth banking and preservation of dental stem cells is promising. Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run.
PubMed: 28616151
DOI: 10.1177/2041731417702531 -
Clinical Oral Investigations Jan 2024To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy. (Review)
Review
OBJECTIVES
To assess treatment options for the reconstruction of the lost interdental papilla and to evaluate evidence for their efficacy.
METHODS
An electronic search (Medline, Embase and the Cochrane Library Database and OpenGray) and a hand search were carried out to identify all types of studies investigating interdental papilla reconstruction (except for reviews) with a minimum of 3 months follow-up.
RESULTS
Forty-five studies were included in the study including 7 RCTs, 2 cohort studies, 19 case series and 17 case reports. Fifteen studies reported on the use of hyaluronic acid, 6 studies on platelet-rich fibrin, 16 studies on soft tissue grafting, 4 studies on orthodontics and 4 on additional modalities. The most common outcome measures were black triangle dimensions and papillary fill percentage. Meta-analysis was not possible due to the high heterogeneity of the studies.
CONCLUSION
There are various options for interdental papilla reconstruction of which hyaluronic acid injections, PRF, surgical grafting and orthodontics seem to improve outcomes at a minimum 3 months. The use of soft tissue grafting with sub-epithelial connective tissue graft seems to be associated with the most robust evidence for the longer-term reduction of 'black triangles'. There is insufficient evidence to make recommendations to clinicians. Further research is needed in the form of well conducted RCTs with longer follow ups and patient reported outcome measures.
CLINICAL RELEVANCE
Patients frequently complain about the appearance of black triangles and their management options seem unclear. This systematic review provides insight into the available reconstructive options.
Topics: Humans; Gingiva; Hyaluronic Acid; Dental Care; Electronics
PubMed: 38231354
DOI: 10.1007/s00784-023-05409-0 -
World Journal of Stem Cells Mar 2023For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth... (Review)
Review
For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.
PubMed: 37007456
DOI: 10.4252/wjsc.v15.i3.31 -
International Journal of Molecular... Feb 2022Both the dental pulp and the apical papilla represent a promising source of mesenchymal stem cells for regenerative endodontic protocols. The aim of this study was to...
Both the dental pulp and the apical papilla represent a promising source of mesenchymal stem cells for regenerative endodontic protocols. The aim of this study was to outline molecular biological conformities and differences between dental pulp stem cells (DPSC) and stem cells from the apical papilla (SCAP). Thus, cells were isolated from the pulp and the apical papilla of an extracted molar and analyzed for mesenchymal stem cell markers as well as multi-lineage differentiation. During induced osteogenic differentiation, viability, proliferation, and wound healing assays were performed, and secreted signaling molecules were quantified by enzyme-linked immunosorbent assays (ELISA). Transcriptome-wide gene expression was profiled by microarrays and validated by quantitative reverse transcription PCR (qRT-PCR). Gene regulation was evaluated in the context of culture parameters and functionality. Both cell types expressed mesenchymal stem cell markers and were able to enter various lineages. DPSC and SCAP showed no significant differences in cell viability, proliferation, or migration; however, variations were observed in the profile of secreted molecules. Transcriptome analysis revealed the most significant gene regulation during the differentiation period, and 13 biomarkers were identified whose regulation was essential for both cell types. DPSC and SCAP share many features and their differentiation follows similar patterns. From a molecular biological perspective, both seem to be equally suitable for dental pulp tissue engineering.
Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Papilla; Dental Pulp; Mesenchymal Stem Cells; Osteogenesis; Stem Cells
PubMed: 35269758
DOI: 10.3390/ijms23052615 -
Stem Cells International 2020Oral mesenchymal stem/progenitor cells (MSCs) are renowned in the field of tissue engineering/regeneration for their multilineage differentiation potential and easy... (Review)
Review
Oral mesenchymal stem/progenitor cells (MSCs) are renowned in the field of tissue engineering/regeneration for their multilineage differentiation potential and easy acquisition. These cells encompass the periodontal ligament stem/progenitor cells (PDLSCs), the dental pulp stem/progenitor cells (DPSCs), the stem/progenitor cells from human exfoliated deciduous teeth (SHED), the gingival mesenchymal stem/progenitor cells (GMSCs), the stem/progenitor cells from the apical papilla (SCAP), the dental follicle stem/progenitor cells (DFSCs), the bone marrow mesenchymal stem/progenitor cells (BM-MSCs) from the alveolar bone proper, and the human periapical cyst-mesenchymal stem cells (hPCy-MSCs). Apart from their remarkable regenerative potential, oral MSCs possess the capacity to interact with an inflammatory microenvironment. Although inflammation might affect the properties of oral MSCs, they could inversely exert a multitude of immunological actions to the local inflammatory microenvironment. The present review discusses the current understanding about the immunomodulatory role of oral MSCs both in periodontitis and systemic diseases, their "double-edged sword" uniqueness in inflammatory regulation, their affection of the immune system, and the underlying mechanisms, involving oral MSC-derived extracellular vesicles.
PubMed: 32184830
DOI: 10.1155/2020/1327405 -
Stem Cells International 2022Tertiary dentin results from the interplay between the host defense and dental injury or infection. Modern endodontics aiming vital pulp treatment take the tertiary... (Review)
Review
Tertiary dentin results from the interplay between the host defense and dental injury or infection. Modern endodontics aiming vital pulp treatment take the tertiary dentin formation as the interim step, with the final goal of a physiological pulp-dentin like tissue regeneration. Dental pulp stem cells have been nominated for contributing to differentiating into odontoblast-like cells who are responsible for reparative dentin formation. Understanding the original dentin formation mechanism provides us a blueprint while exploring the reparative dentin formation mechanism builds bridge to bonafide pulp-dentin tissue regeneration. Among all the regulators, growth factors have long been revealed under the spotlight. The insulin-like growth factor (IGF) family has been implicated in critical events of inducing dentin formation, which is essential for pulp treatment. The expression of IGF family members including IGF1, IGF1R, IGF2, and IGF2R has been well characterized in dental papilla cells, dental pulp stem cells, and periodontal ligament cells. Recent studies indicated IGF binding to the receptors activated pathways, including MAPK pathway, and AKT pathway, orchestrated proliferation, and differentiation, and finally, contributed to dentin formation. This review summarizes the role of IGF family in dentin formation during tooth development and tertiary dentin formation during dentin-pulp repair and sheds light on key parts of research for future treatment improvements.
PubMed: 35432548
DOI: 10.1155/2022/3737346 -
Bioengineering (Basel, Switzerland) Dec 2022The teeth, made up of hard and soft tissues, represent complex functioning structures of the oral cavity, which are frequently affected by processes that cause... (Review)
Review
The teeth, made up of hard and soft tissues, represent complex functioning structures of the oral cavity, which are frequently affected by processes that cause structural damage that can lead to their loss. Currently, replacement therapy such as endodontics or implants, restore structural defects but do not perform any biological function, such as restoring blood and nerve supplies. In the search for alternatives to regenerate the dental pulp, two alternative regenerative endodontic procedures (REP) have been proposed: (I) cell-free REP (based in revascularization and homing induction to remaining dental pulp stem cells (DPSC) and even stem cells from apical papilla (SCAP) and (II) cell-based REP (with exogenous cell transplantation). Regarding the last topic, we show several limitations with these procedures and therefore, we propose a novel regenerative approach in order to revitalize the pulp and thus restore homeostatic functions to the dentin-pulp complex. Due to their multifactorial biological effects, the use of mesenchymal stem cells (MSC)-derived secretome from non-dental sources could be considered as inducers of DPSC and SCAP to completely regenerate the dental pulp. In partial pulp damage, appropriate stimulate DPSC by MSC-derived secretome could contribute to formation and also to restore the vasculature and nerves of the dental pulp.
PubMed: 36671576
DOI: 10.3390/bioengineering10010004