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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 -
RNA Biology Dec 2021Stem cells are a class of undifferentiated cells with great self-renewal and differentiation capabilities that can differentiate into mature cells in specific tissue... (Review)
Review
Stem cells are a class of undifferentiated cells with great self-renewal and differentiation capabilities that can differentiate into mature cells in specific tissue types. Stem cell differentiation plays critical roles in body homoeostasis, injury repair and tissue generation. The important functions of stem cell differentiation have resulted in numerous studies focusing on the complex molecular mechanisms and various signalling pathways controlling stem cell differentiation. Circular RNAs (circRNAs) are a novel class of noncoding RNAs with a covalently closed structure present in eukaryotes. Numerous studies have highlighted important biological functions of circRNAs, and they play multiple regulatory roles in various physiological and pathological processes. Importantly, multiple lines of evidence have shown the abnormal expression of numerous circRNAs during stem cell differentiation, and some play a role in regulating stem cell differentiation, highlighting the role of circRNAs as novel biomarkers of stem cell differentiation and novel targets for stem cell-based therapy. In this review, we systematically summarize and discuss recent advances in our understanding of the roles and underlying mechanisms of circRNAs in modulating stem cell differentiation, thus providing guidance for future studies to investigate stem cell differentiation and stem cell-based therapy. CircRNAs: circular RNAs; ESCs: embryonic stem cells; ADSCs: adipose-derived mesenchymal stem cells; ecircRNAs: exonic circRNAs; EIciRNAs: exon-intron circRNAs; eiRNAs: circular intronic RNAs; tricRNAs: tRNA intronic circRNAs; pol II: polymerase II; snRNP: small nuclear ribonucleoprotein; m6A: N6-methyladenosine; AGO2: Argonaute 2; RBPs: RNA-binding proteins; MBNL: muscleblind-like protein 1; MSCs: mesenchymal stem cells; hiPSCs: human induced pluripotent stem cells; hiPSC-CMs: hiPSC-derived cardiomyocytes; hBMSCs: human bone marrow mesenchymal stem cells; hADSCs: human adipose-derived mesenchymal stem cells; hDPSCs: human dental pulp stem cells; RNA-seq: high-throughput RNA sequencing; HSCs: haematopoietic stem cells; NSCs: neural stem cells; EpSCs: epidermal stem cells; hESCs: human embryonic stem cells; mESCs: murine embryonic stem cells; MNs: motor neurons; SSUP: small subunit processome; BMSCs: bone marrow-derived mesenchymal stem cells; OGN: osteoglycin; GIOP: glucocorticoid‑induced osteoporosis; CDR1as: cerebellar degeneration-related protein 1 transcript; SONFH: steroid-induced osteogenesis of the femoral head; rBMSCs: rat bone marrow-derived mesenchymal stem cells; QUE: quercetin; AcvR1b: activin A receptor type 1B; BSP: bone sialoprotein; mADSCs: mouse ADSCs; PTBP1: polypyrimidine tract-binding protein; ER: endoplasmic reticulum; hUCMSCs: MSCs derived from human umbilical cord; MSMSCs: maxillary sinus membrane stem cells; SCAPs: stem cells from the apical papilla; MyoD: myogenic differentiation protein 1; MSTN: myostatin; MEF2C: myocyte enhancer factor 2C; BCLAF1: BCL2-associated transcription factor 1; EpSCs: epidermal stem cells; ISCs: intestinal stem cells; NSCs: neural stem cells; Lgr5+ ISCs: crypt base columnar cells; ILCs: innate lymphoid cells.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Embryonic Stem Cells; Genetic Markers; Homeostasis; Humans; RNA, Circular; Regenerative Medicine
PubMed: 33896374
DOI: 10.1080/15476286.2021.1913551 -
Journal of Periodontology Jul 2021The new classification of periodontal diseases recognizes the key role of the interdental clinical attachment for defining the periodontal status and the extent of...
The new classification of periodontal diseases recognizes the key role of the interdental clinical attachment for defining the periodontal status and the extent of disease severity. Regenerating interdental clinical attachment not only improves the prognosis of the tooth, but it also lessens the severity of the disease condition. This manuscript provides a state-of-the-art review on surgical reconstructive approaches for treating papillary deficiency associated with soft and hard tissue interproximal defects. Combination therapy of papilla preservation, connective tissue grafting, and coronally advanced flaps may result in regeneration of the intrabony defect coupled with root coverage. Future research highlighted here may have the potential, especially in combination approaches, to repair challenging interproximal soft and hard tissue deficiencies.
Topics: Connective Tissue; Gingiva; Gingival Recession; Guided Tissue Regeneration, Periodontal; Humans; Periodontal Attachment Loss; Plastic Surgery Procedures; Regeneration; Surgical Flaps; Treatment Outcome
PubMed: 33152103
DOI: 10.1002/JPER.20-0587 -
Journal of Clinical Periodontology Jun 2022To assess the beneficial and adverse effects on the dental and periodontal issues of periodontal-orthodontic treatment of teeth with pathological tooth flaring,... (Meta-Analysis)
Meta-Analysis Review
Effect of periodontal-orthodontic treatment of teeth with pathological tooth flaring, drifting, and elongation in patients with severe periodontitis: A systematic review with meta-analysis.
AIM
To assess the beneficial and adverse effects on the dental and periodontal issues of periodontal-orthodontic treatment of teeth with pathological tooth flaring, drifting, and elongation in patients with severe periodontitis.
MATERIALS AND METHODS
Nine databases were searched in April 2020 for randomized/non-randomized clinical studies. After duplicate study selection, data extraction, and risk-of-bias assessment, random-effect meta-analyses of mean differences (MDs) and their 95% confidence intervals (CIs) were performed, followed by subgroup/meta-regression analyses.
RESULTS
A total of 30 randomized and non-randomized clinical studies including 914 patients (29.7% male; mean age 43.4 years) were identified. Orthodontic treatment of pathologically migrated teeth was associated with clinical attachment gain (-0.24 mm; seven studies), pocket probing depth reduction (-0.23 mm; seven studies), marginal bone gain (-0.36 mm; seven studies), and papilla height gain (-1.42 mm; two studies) without considerable adverse effects, while patient sex, gingival phenotype, baseline disease severity, interval between periodontal and orthodontic treatment, and orthodontic treatment duration affected the results. Greater marginal bone level gains were seen by additional circumferential fiberotomy (two studies; MD = -0.98 mm; 95% CI = -1.87 to -0.10 mm; p = .03), but the quality of evidence was low.
CONCLUSIONS
Limited evidence of poor quality indicates that orthodontic treatment might be associated with small improvements of periodontal parameters, which do not seem to affect prognosis, but more research is needed.
Topics: Female; Humans; Male; Periodontitis
PubMed: 34327710
DOI: 10.1111/jcpe.13529 -
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 -
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 -
Life (Basel, Switzerland) Feb 2024Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone... (Review)
Review
Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.
PubMed: 38541613
DOI: 10.3390/life14030287 -
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