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International Journal of Oral Science Oct 2023Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a...
Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.
Topics: Animals; Humans; Rats; Cell Differentiation; Intracellular Signaling Peptides and Proteins; Leukemia; Mesenchymal Stem Cells; Neurogenesis; Stem Cells; Transcription Factor HES-1
PubMed: 37852994
DOI: 10.1038/s41368-023-00253-0 -
Stem Cells International 2020Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage... (Review)
Review
Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.
PubMed: 32952572
DOI: 10.1155/2020/8864572 -
PeerJ 2023Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue... (Review)
Review
Dental-derived stem cells have excellent proliferation ability and multi-directional differentiation potential, making them an important research target in tissue engineering. An increasing number of dental-derived stem cells have been discovered recently, including dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHEDs), stem cells from apical papilla (SCAPs), dental follicle precursor cells (DFPCs), and periodontal ligament stem cells (PDLSCs). These stem cells have significant application prospects in tissue regeneration because they are found in an abundance of sources, and they have good biocompatibility and are highly effective. The biological functions of dental-derived stem cells are regulated in many ways. Epigenetic regulation means changing the expression level and function of a gene without changing its sequence. Epigenetic regulation is involved in many biological processes, such as embryonic development, bone homeostasis, and the fate of stem cells. Existing studies have shown that dental-derived stem cells are also regulated by epigenetic modifications. Pulp and periodontal regeneration refers to the practice of replacing damaged pulp and periodontal tissue and restoring the tissue structure and function under normal physiological conditions. This treatment has better therapeutic effects than traditional treatments. This article reviews the recent research on the mechanism of epigenetic regulation of dental-derived stem cells, and the core issues surrounding the practical application and future use of pulp and periodontal regeneration.
Topics: Humans; Mesenchymal Stem Cells; Epigenesis, Genetic; Stem Cells; Periodontal Ligament; Periodontium
PubMed: 36620748
DOI: 10.7717/peerj.14550 -
Journal of Pharmacy & Bioallied Sciences Aug 2020Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are... (Review)
Review
Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are explored by limited studies and their molecular insights are very rarely studied. This systematic review is aimed to provide the best scientific literature source on the molecular insights into odontogenesis in hyperglycemic environment caused by diabetes mellitus or by maternal diabetes on the offspring. The literature search was conducted on the databases, namely PubMed, PubMed Central, Cochrane, and Scopus. The original studies exploring the alterations in the molecular pathways of odontogenesis in diabetes mellitus were selected. Data were extracted, chosen, and evaluated by two independent researchers. At the end of thorough data search, four articles were eligible for the review. Three articles brought out the molecular pathways involved in the offspring of gestational diabetes through animal models. Fourth article was an study, which treated the stem cells in hyperglycemic environment and drafted the molecular pathway. The altered molecular pathways in dental epithelial stem cells (DESCs), dental papilla cells (DPCs), and stem cells from apical papilla were studied and empowered with statistical analysis. Thus with this systematic review, we conclude that apurinic/apyrimidinic endonuclease1 downregulation causing deoxyribonucleic acid hypermethylation and gene silencing, activation of toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway are involved in suppressing cell proliferation and accelerated apoptosis in DESCs in high glucose environment. DPCs are suppressed from odonto differentiation by activation of TLR4 signaling and resulting inhibition of SMAD1/5/9 phosphorylation in diabetic condition. NF-κB pathway activation causes decreased cell proliferation and enhanced differentiation in apical papilla stem cells in hyperglycemia. Further studies targeting various stages of odontogenesis can reveal more molecular insight.
PubMed: 33149430
DOI: 10.4103/jpbs.JPBS_159_20 -
Journal of Indian Society of... 2022The regeneration and maintenance of the interdental papilla presents a great challenge to the clinician while smile designing. Proportions of papilla height (PH),...
BACKGROUND
The regeneration and maintenance of the interdental papilla presents a great challenge to the clinician while smile designing. Proportions of papilla height (PH), crestal PH (CPH), and proximal contact areas (PCA) are more stable parameters.
AIM
The purpose of the present study was to evaluate and correlate the papilla proportion (PP), crestal PP (CPP), and PCA proportion (PCAP) in periodontally healthy males and females.
MATERIALS AND METHODS
One hundred and twenty patients in an age group of 20-40 years, divided equally based on gender, were assessed for PH, CPH, and PCA of maxillary anterior teeth. The findings were recorded on study models and radiographs to obtain the PP, CPP, and PCAP on the mesial and distal aspects of respective tooth.
STATISTICAL ANALYSIS
The overall comparison of parameters was performed using paired -test.
RESULTS
The mean mesial PP (43.51% ± 3.10% for male and 45.23% ± 2.23% for female) and CPP values (48.36% ± 3.35% for male and 51.16% ± 2.96% for female) were found to be greater of each tooth type and were more pronounced for females. The PCAP values were greater for distal aspects (36.76% ± 7.00% for males and 33.30% ± 6.93% for females).
CONCLUSION
The results of the study indicate that PP and CPP are more pronounced in females, while the PCAP is more marked in males. Furthermore, it appears that the PP and CPP are inversely related to the PCAP in both males and females.
PubMed: 36339384
DOI: 10.4103/jisp.jisp_251_21 -
Cells Sep 2022Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells.... (Review)
Review
Stem cells are a well-known autologous pluripotent cell source, having excellent potential to develop into specialized cells, such as brain, skin, and bone marrow cells. The oral cavity is reported to be a rich source of multiple types of oral stem cells, including the dental pulp, mucosal soft tissues, periodontal ligament, and apical papilla. Oral stem cells were useful for both the regeneration of soft tissue components in the dental pulp and mineralized structure regeneration, such as bone or dentin, and can be a viable substitute for traditionally used bone marrow stem cells. In recent years, several studies have reported that plant extracts or compounds promoted the proliferation, differentiation, and survival of different oral stem cells. This review is carried out by following the PRISMA guidelines and focusing mainly on the effects of bioactive compounds on oral stem cell-mediated dental, bone, and neural regeneration. It is observed that in recent years studies were mainly focused on the utilization of oral stem cell-mediated regeneration of bone or dental mesenchymal cells, however, the utility of bioactive compounds on oral stem cell-mediated regeneration requires additional assessment beyond in vitro and in vivo studies, and requires more randomized clinical trials and case studies.
Topics: Bone Marrow Cells; Mesenchymal Stem Cells; Periodontal Ligament; Plant Extracts; Stem Cells
PubMed: 36139367
DOI: 10.3390/cells11182792 -
The Chinese Journal of Dental Research Sep 2021Tooth eruption is closely linked to the normal development of dentition and proper establishment of occlusion. Disturbances in tooth eruption may affect oral... (Review)
Review
Tooth eruption is closely linked to the normal development of dentition and proper establishment of occlusion. Disturbances in tooth eruption may affect oral physiological functions, facial contour and aesthetics; it is therefore important to understand the eruption process. This process is a complex biological event involving dynamic changes at the tissue and cellular levels. It is guided by anatomical structures as well as biological and molecular factors that result in the movement of the tooth to its final functional position in the oral cavity. Evidence increasingly suggests that stem cells contribute to tooth development and eruption. Multiple stem cell populations have been discovered in teeth and in their supporting tissues, such as dental follicle precursor cells, orofacial bone-/bone marrow-derived mesenchymal stem cells, periodontal ligament stem cells, stem cells from the apical papilla and dental pulp stem cells. These stem cells exhibit distinct differentiation capacities and are closely linked to alveolar bone remodelling, periodontium development and root formation during the eruption process. The present review summarises the current knowledge of the characteristics and functions of orofacial stem cells in tooth eruption, with a particular focus on recent discoveries concerning their lineage allocation and regulatory mechanisms.
Topics: Cell Differentiation; Periodontal Ligament; Stem Cells; Tooth; Tooth Eruption
PubMed: 34491008
DOI: 10.3290/j.cjdr.b1965049 -
Frontiers in Genetics 2021Mesenchymal stem cells (MSCs) are promising seed cells in tissue repair and regeneration due to their featured properties of self-renewal and multipotency. However, a... (Review)
Review
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.
PubMed: 34764982
DOI: 10.3389/fgene.2021.750990 -
Stem Cell Research & Therapy May 2020Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem... (Review)
Review
BACKGROUND
Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem cells. Recently, dental tissue-derived cells have been used clinically due to their great potential, easy accessibility, and ability to be obtained via methods with low invasiveness. The aim of this study is to systematically assess the clinical effectiveness of dental cell-mediated therapies compared to current evidence-based methods in human patients.
METHODS
The electronic databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched up to December 2019 for clinical trials. Clinical trials with any intervention using stem cells/cells derived from dental tissue were included.
RESULTS
A total of 815 studies were identified by the electronic search, and 38 articles qualified for full-text evaluation. Finally, 20 studies (10 clinical trials using dental pulp-derived cells, 3 clinical trials using periodontal ligament-derived cells, and 7 studies using gingiva-derived cells) were included in this review. No clinical trials using dental follicle- or apical papilla-derived cells were selected in this review. Dental pulp-derived cells were used in clinical trials for bone regeneration, periodontitis, and dental pulp regeneration. All clinical trials using periodontal ligament-derived cells and gingiva-derived cells were conducted for periodontal disease treatment and gingival augmentation, respectively. Among the 20 selected studies, 16 showed clinical benefits of cell transplantation therapies. In addition, no study reported adverse events that may have been associated with cell transplantation.
CONCLUSIONS
These findings indicate that dental tissue-derived cells would be useful for cell-based regenerative medicine for various diseases.
Topics: Clinical Trials as Topic; Dental Pulp; Gingiva; Humans; Mesenchymal Stem Cells; Periodontal Ligament; Regenerative Medicine
PubMed: 32398041
DOI: 10.1186/s13287-020-01683-x -
Frontiers in Cell and Developmental... 2021Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These...
Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 . Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.
PubMed: 34901015
DOI: 10.3389/fcell.2021.769193