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Neural crest cells give rise to multiple cell types and demonstrate the origin and differentiation potentials of dental stem cells. 1 -5: The formation of neural crest cells; 6: Dental stem cells; the dotted arrow shows the differentiation potential of dental stem cells; 7: Adipocytes; 8: Osteoblasts and chondrocytes; 9: Neurons.
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Over the past few decades, scientific research into neural crest-derived stem cells has progressed rapidly. The migration and differentiation of neural crest-derived stem cells has been an interesting area of research. Stem cells within teeth originating from the embryonic neural crest have attracted increasing attention in clinical and scientific...
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Context 1
... crest cells undergo an epithelial-to-mesenchymal transformation (EMT), after which they migrate to different locations and differentiate into different cells and tissues. In vivo and in vitro experiments revealed that neural crest cells give rise to multiple cell types (Fig 3), including adipocytes 12 , neurons 13 , glias 14,15 , smooth muscle, chondrocytes, osteoblasts 16 , dentine (odontoblasts) 8 , and melanocytes 17 . Neural crest cells are defined because of their origin; they are multipotent and self-renewable [18][19][20][21][22][23] . ...
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Background:
The proteomic signature or profile best describes the functional component of a cell during its routine metabolic and survival activities. Additional complexity in differentiation and maturation is observed in stem/progenitor cells. The role of functional proteins at the cellular level has long been attributed to anatomical niches, and...
Citations
... DPSCs share similarities with bone marrow MSCs and express markers related to mineralization and osteogenesis (Chen et al., 2005;Ching et al., 2017). With proper induction, dental pulp stem cells can differentiate into osteoblasts, chondrocytes, adipocytes, and neural-like cells (Zhu et al., 2018) (Figure 2). In a study conducted by Alge et al. (2010), DPSCs demonstrated a higher proliferation rate and greater clonal potential compared to bone marrow MSCs. ...
Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.
... 'Domain III' or 'FC domain': A spherical domain present at the carboxyl terminal, which is a common feature of the FBLN family. [7][8][9] 'Domain II': Variable number of calcium-binding epithelial growth factor modules. 'Domain I': Variable region at the end of the amino group. FBLN s are classified into two subgroups based on the overall protein structure. ...
To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC‐mediated bone regeneration. It was showed that there was an m⁶A methylation site in 3′UTR of FBLN1 mRNA, and the mutation of the m⁶A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m⁶A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR‐615‐3p negatively regulated FBLN1 by binding FBLN1 3′UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC‐mediated bone regeneration. Then, we discovered miR‐615‐3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m⁶A‐miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615‐3p mediated the decay of FBLN1 mRNA which facilitated by m⁶A reading protein YTHDF2. This provided a novel m⁶A‐miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration.
... Recent research has demonstrated that DPSCs can differentiate into various cell types, including odontoblasts, adipocytes, osteoblasts, neuronal cells, chondrocytes, muscle cells, hepatocytes, and pancreatic cells, in response to specific induction cues [42][43][44][45] ( Figure 2). However, the differentiation potential of DPSCs is governed by gene expression profiles [46]. For example, DPSCs isolated from permanent teeth are more prone to neuronal lineage differentiation, whereas SHED exhibits superior differentiation potential toward bone and adipose tissue [47]. ...
Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
... Degrading enzymes MMP MMP-1 and -8 degrade type III collagen to ensure normal dentin (Zhou et al. 2015). MMP20 is involved in the organic matrix tissue during dentin formation (Wiesen et al. 2015); MMP3 can induce differentiation of embryonic stem cells into odontoblasts Extracellular matrix vesicles Induction and promotion of odontogenic differentiation of receptor stem cells (Mazzoni et al. 2015); The stromal vesicles in the dentin layer can promote the biogenesis and dentin mineralization (Chen et al. 2021); Mineralization in which MV participates mainly occurs in the dentine mask, which interacts with ECM macromolecules to degrade collagen and promote dentin mineralization (Zhu et al. 2018). ...
... As a form of EVs, exosomes play an essential regulatory role in tooth differentiation and tooth regeneration (Jiang et al. 2017;Zhu et al. 2018). The exosomes derived from hDPSCs have been reported to promote odontogenic differentiation of hDPSCs and hBMSCs by activating the P38 MAPK pathway . ...
Dental defects and loss are common oral diseases that seriously affect the chewing efficiency of patients and thereby affect their health. With the development of tissue engineering technology, dental tissue regeneration has emerged as a promising technique. Cell type, extracellular matrix (ECM) environment, cytokines and other factors which affect odontogenic differentiation and dental tissue regeneration have aroused significant interest. The functional ECM consists of extracellular components that control the initiation and growth of crystal deposition and regulate the differentiation and regeneration of endogenous or exogenous stem cells in the defect site. At present, the function and regulatory mechanism of the functional ECM in this process remain poorly understood. Therefore, elucidating the effect of the functional ECM on odontogenic differentiation and its mechanism has great scientific significance and potential clinical application. This review explored functional ECM components involved in odontogenic differentiation and dental tissue regeneration.
... Of which, DSC-EVs draw particular attention for their embryonic neural crest origin. 20,21 Comparing the PIWI-interacting RNAs in DSC-EVs and EVs from bone marrow mesenchymal stem cells, more neuronal information was found enriched in DSC-EVs. 22 In this regard, it has also been suggested recently that DSC-EVs presented superior therapeutic potential in neurological diseases and thus may serve as better candidates for related therapy. ...
Traumatic brain injury (TBI) contributes to the key causative elements of neurological deficits. However, no effective therapeutics have been developed yet. In our previous work, extracellular vesicles (EVs) secreted by stem cells from human exfoliated deciduous teeth (SHED) offered new insights as potential strategies for functional recovery of TBI. The current study aims to elucidate the mechanism of action, providing novel therapeutic targets for future clinical interventions. With the miRNA array performed and Real-time PCR validated, we revealed the crucial function of miR-330-5p transferred by SHED-derived EVs (SHED-EVs) in regulating microglia, the critical immune modulator in central nervous system. MiR-330-5p targeted Ehmt2 and mediated the transcription of CXCL14 to promote M2 microglia polarization and inhibit M1 polarization. Identified in our in vivo data, SHED-EVs and their effector miR-330-5p alleviated the secretion of inflammatory cytokines and resumed the motor functional recovery of TBI rats. In summary, by transferring miR-330-5p, SHED-EVs favored anti-inflammatory microglia polarization through Ehmt2 mediated CXCL14 transcription in treating traumatic brain injury.
... ability and differentiation potential, be able to establish stable cell lines, and have the lowest possible antigenicity [9][10][11]. MSCs have been widely applied in regenerative medicine research because of their abundance, strong proliferation ability and immunomodulatory function [12][13][14][15][16]. ...
Background
In tissue engineering, mesenchymal stem cells (MSCs) are common seed cells because of abundant sources, strong proliferation ability and immunomodulatory function. Numerous researches have demonstrated that MSC-macrophage crosstalk played a key role in the tissue engineering. Macrophages could regulate the differentiation of MSCs via different molecular mechanisms, including extracellular vesicles. Apoptotic macrophages could generate large amounts of apoptotic vesicles (apoVs). ApoVs are rich in proteins, RNA (microRNAs, mRNAs, ncRNAs, etc.) and lipids, and are a key intercellular communication mediator that can exert different regulatory effects on recipient cells. MiRNAs account for about half of the total RNAs of extracellular vesicles, and play important roles in biological processes such as cell proliferation and differentiation, whereas the functions of macrophage-derived apoVs remain largely unknown. There was no research to clarify the role of macrophage-derived apoVs in MSC fate choices. In this study, we aimed to characterize macrophage-derived apoVs, and investigate the roles of macrophage-derived apoVs in the fate commitment of MSCs.
Methods
We characterized macrophage-derived apoVs, and investigated their role in MSC osteogenesis and adipogenesis in vitro and in vivo. Furthermore, we performed microRNA loss- and gain-of-function experiments and western blot to determine the molecular mechanism.
Results
Macrophages could produce a large number of apoVs after apoptosis. MSCs could uptake apoVs. Then, we found that macrophage-derived apoVs inhibited osteogenesis and promoted adipogenesis of MSCs in vitro and in vivo. In mechanism, apoVs were enriched for microRNA155 (miR155), and apoVs regulated osteogenesis and adipogenesis of MSCs by delivering miR155. Besides, miR155 regulated osteogenesis and adipogenesis of MSCs cultured with macrophage-derived apoVs via the SMAD2 signaling pathway.
Conclusions
Macrophage-derived apoVs could regulate the osteogenesis and adipogenesis of MSCs through delivering miR155, which provided novel insights for MSC-mediated tissue engineering.
... Dentin-pulp complex is considered to be one organ as they both share the same origin from mesoderm [7]. Moreover, there are anatomic and physiologic relations between dentin and pulp; as dentin is the protective tissue for the dental pulp, and in the meantime, the pulp is the source of nutrition for the dentin [8]. ...
The objective of this study is to compare the estimated values of remaining dentin thickness (RDT) recorded by a newly introduced electrical impedance device (Prepometer) with cone beam computed tomography (CBCT) and histological in situ measurement. A total number of thirty human molars were used in this study. A deep class I cavity was prepared. The RDT for each cavity was measured with Prepometer in three different points (mesial, middle, and distal). Same specimens were imaged with high-resolution Cone Beam Computed Tomography CBCT (0.1 mm voxel size) using I CAT next Generation Machine (Imaging Science International, Hatfield, PA, USA), to provide the highest possible accuracy of linear measurements. Finally, the specimens were vertically sectioned parallel to the long axis of the tooth in a mesiodistal direction splitting the cavity into two halves through its center. Then, the actual RDT of each half will be measured in the same three points using a digital caliper. The outcome of one-way ANOVA revealed that there was no significant difference in RDT values measured by prepometer device, CBCT, or histological sectioning methods (p > 0.05). Within the limitations of this laboratory study, prepometer seems to be a potential non-invasive accurate measuring tool for RDT. Based on the findings of this study, the Prepometer can be considered as an easily handled and less-expensive method compared to CBCT to evaluate the RDT. Also, it can be used in dental schools and with less-experienced operators to avoid traumatic exposures of the dental pulp.
... Although there is not a reported protein expression data, Wang et al. showed the similar gene expression patterns of NMP-derived MSCs and Bone Marrow Stem Cells (BMSCs) [53]. We preferred to use DPSCs because of their neural crest origin [58] during embryonic development which might resemble to NMP derived MSC population compared to other sources. Although cytokine array revealed a differential protein expression profile, some of the proteins such as GM-CSF, GROα and IL-10 which are secreted by or act on MSCs [28,30,40]; [49], were both upregulated in DPSCs and NMP-derived MSCs. ...
Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic development, neuromesodermal progenitors (NMPs), reside in the primitive streak during development, is known to differentiate into paraxial mesoderm. In the current study, we generated NMPs from human embryonic stem cells (hESC), subsequently derived MSCs and characterized this cell population in vitro and in vivo. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for in vitro and in vivo research.
Graphical abstract
... It involves three crucial components: seed cells, scaffolds, and bioactive molecules(6-8). Seed cells should have self-renewal ability and differentiation potential, be able to establish stable cell lines, and have the lowest possible antigenicity (9)(10)(11). MSCs have been widely applied in regenerative medicine research because of their abundance, strong proliferation ability and immunomodulatory function (12)(13)(14)(15)(16). extensive apoptosis occurred soon after stem cell transplantation, and a large number of apoptotic bodies were released, enhancing angiogenesis and having a therapeutic effect (30). ...
Background
In tissue engineering, mesenchymal stem cells (MSCs) are common seed cells because of abundant sources, strong proliferation ability and immunomodulatory function. Numerous researches have demonstrated that MSC-macrophage crosstalk played a key role in the tissue engineering. Macrophages could regulate the differentiation of MSCs via different molecular mechanisms, including extracellular vesicles. Apoptotic macrophages could generate large amounts of apoptotic vesicles (apoVs), whereas the functions of macrophage-derived apoVs remain largely unknown. There was no research to clarify the role of macrophage-derived apoVs in MSC fate choices. In this study, we aimed to characterize macrophage-derived apoVs, and investigate the roles of macrophage-derived apoVs in the fate commitment of MSCs.
Methods
We characterized macrophage-derived apoVs, and investigated their role in MSC osteogenesis and adipogenesis in vitro and in vivo. Furthermore, we performed microRNA loss- and gain- of function experiments and western blot to determine the molecular mechanism.
Results
We found that macrophage-derived apoVs inhibited osteogenesis and promoted adipogenesis in vitro and in vivo. In mechanism, apoVs regulated osteogenesis and adipogenesis of MSCs by delivering microRNA155 (miR155).
Conclusions
Macrophage-derived apoVs could regulate the osteogenesis and adipogenesis of MSCs through delivering miR155, which provided novel insights for MSC-mediated tissue engineering.
... DFPCs were first isolated from the dental follicle surrounding the impacted third molar tooth germ and identified by Morsczeck et al. (2005). DFPCs not only have better immunomodulatory and anti-apoptotic effects on the immune system than DPSCs and SHED, but also exhibit greater osteogenic properties than SHED and DPSCs as the osteogenic-related markers such as Runx2 and DSPP are highly expressed in DFPCs (Zhu et al., 2018). In addition, DFPCs were able to differentiate into cementoblasts in vivo (Handa et al., 2002). ...
Mesenchymal stem cells (MSCs) are promising seed cells in tissue repair and regeneration due to their featured properties of self-renewal and multipotency. However, a growing body of evidence has demonstrated that MSCs exert biological functions mainly through secreting exosomes. Exosomes, which contain RNA, proteins, lipids, and metabolites, are new players in regulating many fundamental processes and play important roles in regenerative medicine. Exosomes not only mimic the effects of their parent cells but also possess many advantages such as high drug loading capacity, low immunogenicity, excellent biocompatibility, and low side effects. Currently, a total of 6 different dental stem cells (DSCs) including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor cells (DFPCs), stem cells from apical papilla (SCAPs) and gingival mesenchymal stem cells (GMSCs) have been isolated and identified. DSC-derived exosomes (DSC-Exos) are actively involved in intercellular communication, anti-inflammation, osteogenesis, angiogenesis, immunomodulation, nurturing neurons, and promoting tumor cell apoptosis. In this review, we will critically review the emerging role and clinical application potential of DSC-Exos.
