Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery...Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.展开更多
BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,...BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling ...BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.展开更多
Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we use...Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.展开更多
Peripheral nerve injury(PNI)seriously affects people’s quality of life.Stem cell therapy is considered a promising new option for the clinical treatment of PNI.Dental stem cells,particularly dental pulp stem cells(DP...Peripheral nerve injury(PNI)seriously affects people’s quality of life.Stem cell therapy is considered a promising new option for the clinical treatment of PNI.Dental stem cells,particularly dental pulp stem cells(DPSCs),are adult pluripotent stem cells derived from the neuroectoderm.DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages,such as easy isolation,multidifferentiation potential,low immunogenicity,and low transplant rejection rate.DPSCs are extensively used in tissue engineering and regenerative medicine,including for the treatment of sciatic nerve injury,facial nerve injury,spinal cord injury,and other neurodegenerative diseases.This article reviews research related to DPSCs and their advantages in treating PNI,aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.展开更多
Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engin...Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.展开更多
BACKGROUND Nerve diseases and injuries,which are usually accompanied by motor or sensory dysfunction and disorder,impose a heavy burden upon patients and greatly reduce their quality of life.Dental pulp stem cells(DPS...BACKGROUND Nerve diseases and injuries,which are usually accompanied by motor or sensory dysfunction and disorder,impose a heavy burden upon patients and greatly reduce their quality of life.Dental pulp stem cells(DPSCs),derived from the neural crest,have many characteristics that are similar to those of neural cells,indicating that they can be an ideal source for neural repair.AIM To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery.METHODS DPSCs were isolated,cultured,and identified by multilineage differentiation and flow cytometry.Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction.Then,we collected the secretions of DPSCs.We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays.Finally,we generated a sciatic nerve crush injury model in vivo and used the sciatic function index,walking track analysis,muscle weight,and hematoxylin&eosin(H&E)staining to further evaluate the nerve repair ability of DPSCs.RESULTS DPSCs highly expressed several specific neural markers,including GFAP,S100,Nestin,P75,and NF200,and were inclined toward neural differentiation.Furthermore,neural-induced DPSCs(N-DPSCs)could express neurotrophic factors,including NGF,BDNF,and GDNF.The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells.In vivo,both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy.However,in terms of anatomy and motor function,as shown by H&E staining,immunofluorescent staining,and walking track analyses,the repair effects of N-DPSCs were more sustained,potent,and effective than those of DPSCs and the controls.CONCLUSION In summary,this study demonstrated that DPSCs are inclined to differentiate into neural cells.N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs.Furthermore,our results suggested that NDPSCs could help crushed nerves with functional recovery and anatomical repair in vivo.Thus,DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.展开更多
Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papill...Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papilla,periodontal tissue,bone marrow and peripheral blood,with or without application of scaffolds and growth factors in the root canal space,resulting in cementum-like and bone-like tissue formation.Without the involvement of dental pulp stem cells(DPSCs),it is unlikely that functional pulp regeneration can be achieved,even though acceptable repair can be acquired.DPSCs,due to their specific odontogenic potential,high proliferation,neurovascular property,and easy accessibility,are considered as the most eligible cell source for dentin–pulp regeneration.The regenerative potential of DPSCs has been demonstrated by recent clinical progress.DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp.The self-renewal,proliferation,and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors.Over recent decades,epigenetic modulations implicating histone modifications,DNA methylation,and noncoding(nc)RNAs have manifested as a new layer of gene regulation.These modulations exhibit a profound effect on the cellular activities of DPSCs.In this review,we offer an overview about epigenetic regulation of the fate of DPSCs;in particular,on the proliferation,odontogenic differentiation,angiogenesis,and neurogenesis.We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.展开更多
Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest.They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells bec...Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest.They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic factors.Few studies have reported Alzheimer’s disease treatment using dental pulp stem cells.Rat models of Alzheimer’s disease were established by injecting amyloid-β1–42 into the hippocampus.Fourteen days later,5×106 dental pulp stem cells were injected into the hippocampus.Immunohistochemistry and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin,NeuN,and neurofilament 200 in the hippocampus,while the expression of amyloid-βwas decreased.Moreover,cognitive and behavioral abilities were improved.These findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins,which indicates a potential therapeutic effect for Alzheimer’s disease.This study was approved by the Animal Ethics Committee of Harbin Medical University,China(approval No.KY2017-132)on February 21,2017.展开更多
Aim The aim of this study was to confirm the multilineage differentiation ability of dental pulp stem cells (DPSCs) from green fluorescent protein (GFP) transgenic mice. The expression of GFP in DPSCs was also obs...Aim The aim of this study was to confirm the multilineage differentiation ability of dental pulp stem cells (DPSCs) from green fluorescent protein (GFP) transgenic mice. The expression of GFP in DPSCs was also observed during differentiation. Methodology DPSCs were harvested from the dental pulp tissue of transgenic nude mice, and then transferred to osteogenic, adipogenic, and chondrogenic media. The morphological characterization of induced cells was observed by microscopy and histological staining. The expression of marker genes was measured by RT-PCR. Results The endogenous GFP and multilineage potential of transgenic DPSCs had no influence on each other. Moreover, the results of fluorescence microscopic imaging suggest that there was no significant decline of GFP expression during DPSCs differentiation. Conclusion As the population of GFP labeled DPSCs can be easily identified, this will be a promising method for tracking DPSCs in vivo.展开更多
Dental pulp stem cells are a type of adult stem cells with strong proliferative ability and multi-differentiation potential. There are no studies on treatment of vascular dementia with dental pulp stem cells. In the p...Dental pulp stem cells are a type of adult stem cells with strong proliferative ability and multi-differentiation potential. There are no studies on treatment of vascular dementia with dental pulp stem cells. In the present study, rat models of vascular dementia were established by two-vessel occlusion, and 30 days later, rats were injected with 2 × 10^(7) dental pulp stem cells via the tail vein. At 70 days after vascular dementia induction, dental pulp stem cells had migrated to the brain tissue of rat vascular dementia models and differentiated into neuronlike cells. At the same time, doublecortin, neurofilament 200, and Neu N m RNA and protein expression levels in the brain tissue were increased, and glial fibrillary acidic protein m RNA and protein expression levels were decreased. Behavioral testing also revealed that dental pulp stem cell transplantation improved the cognitive function of rat vascular dementia models. These findings suggest that dental pulp stem cell transplantation is effective in treating vascular dementia possibly through a paracrine mechanism. The study was approved by the Animal Ethics Committee of Harbin Medical University(approval No. KY2017-132) in 2017.展开更多
Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was co...Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.展开更多
Author contributions: Mead B was responsible for study conception and design, collection and^or assembly of data, data analysis and interpretation and manuscript writing. Logan A participated in study conception and ...Author contributions: Mead B was responsible for study conception and design, collection and^or assembly of data, data analysis and interpretation and manuscript writing. Logan A participated in study conception and design, data analysis and interpretation and manuscript writing. Berry M was responsible for manuscript writing. Scheven BA was in charge of study conception and design, data analysis and interpretation and manuscript writing. Leadbeater W participated in study conception and design, data analysis and interpretation and manuscript writing. All authors approved the final version of this paper.展开更多
For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesen...For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesenchymal stem cell(MSC)-like immunophenotypic characteristics,high proliferation rate,potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs.In addition,several main application forms of DPSCs and their derivatives have been investigated,including stem cell injections,modified stem cells,stem cell sheets and stem cell spheroids.In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs.Therefore,DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration.In this review,we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine.We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions.The methodologies for therapeutic administration of DPSCs and their derivatives are introduced,including single injections and the transplantation of the cells with a support,as cell sheets,or as cell spheroids.We also summarize the underlying mechanisms of the regenerative potential of DPSCs.展开更多
The hippocampal formation, important for spatial learn- ing and memory function, exhibits high level of plas- ticity in response to behavioral changes as well as injury. Dysfunction of the hippocampus is one of the ha...The hippocampal formation, important for spatial learn- ing and memory function, exhibits high level of plas- ticity in response to behavioral changes as well as injury. Dysfunction of the hippocampus is one of the hallmark features of neurodegenerative diseases like temporal lobe epilepsy (TLE) and Alzheimer's disease (AD) (Dhanush- kodi and Shetty 2008). Excitotoxicity is one of the known mechanisms by which neurons undergo degeneration in neurodegenerative condition (Haglid et al., 1994; Doble et al., 1995). Brain regions such as hippocampus are more susceptible to excitotoxic damage. During excitotoxicity.展开更多
Objectives: The aim of this review is to explain the role of Dental Pulp Stem Cells (DPSCs) in repairing or regenerating damaged tissue/organs for both systemic and oral diseases and, in addition, review the different...Objectives: The aim of this review is to explain the role of Dental Pulp Stem Cells (DPSCs) in repairing or regenerating damaged tissue/organs for both systemic and oral diseases and, in addition, review the differentiation, isolation of dental pulp stem cells and their applications in regenerative medicine. Materials and Methods: An electronic search was done using Cohchrane, PubMed and Google Scholar. Out of 310 articles, only 25 articles have been selected to be included in this review because it is directly related to the topic and they are matching the inclusion criteria of this review: “Language: English” and “Year: 2006-2016”. Results: DPSCs have been widely used as a mesenchymal stem cells source due to easy accessibility and less invasive harvesting. DPSCs could be used for pulpal regeneration, tooth reconstruction, endocrinology, neurology, angiogenesis and vasculogenises. The most common application of DPSCs in the dental field is pulp regeneration. Conclusion: Stem cell-based therapy holds a great promise to solve health problems from both systemic and oral diseases. Studying in DPSCs grows rapidly;however, there are still questionable issues needed to be optimized and answered such as the variable biological capacity of DPSCs.展开更多
Stem cells were isolated from human dental pulp using an optimized method, in which pulp pieces were digested by enzymes and immobilized to enhance cell outgrowth. Stem cell marker expression was detected by reverse t...Stem cells were isolated from human dental pulp using an optimized method, in which pulp pieces were digested by enzymes and immobilized to enhance cell outgrowth. Stem cell marker expression was detected by reverse transcription-PCR (RT-PCR), and differentiation markers were detected by real-time quantitative RT-PCR and immunocytochemistry. Results showed that dental pulp stem cells actively expressed nanog, oct4, nucleostemin slain-l, jmjdla, jmjd2c, and cyclin DI. When stem cells were induced to differentiate into neurons, nucleostemin, nanog, and cyclin D1 expression significantly decreased, whereas expression of neuronal markers, such as microtubule associated protein-2 and neurofilament-heavy, significantly increased. These results suggested that stem cells exited a pluripotent state and entered a neuronal differentiation pathway. In addition, results demonstrated that human dental pulp serves as a reservoir of stem cells that express defined stem cell markers; these cells were easily isolated and were induced to differentiate towards a desired cell lineage.展开更多
The presence of insufficient bone volume affects the implant healing and success.The aim of this study was to evaluate osteogenic capacity of dental pulp stem cells(DPSCs) on micro-arc oxidation(MAO) titanium surface....The presence of insufficient bone volume affects the implant healing and success.The aim of this study was to evaluate osteogenic capacity of dental pulp stem cells(DPSCs) on micro-arc oxidation(MAO) titanium surface.DPSCs were challenged at MAO and smooth titanium surface separately for different durations,and the bone marrow mesenchymal stem cells(BMSCs) served as the positive controls.The osteogenic capacity of DPSCs on MAO titanium surface was assessed by using scanning electron microscopy,energy dispersive spectroscopy,biochemical tests and real-time quantitative PCR.Data showed that DPSCs differentiated into osteoblasts and expressed bone morphogenetic genes on MAO titanium surface.The results of this study revealed that DPSCs had good potential to generate mineralized tissue on MAO titanium plates.The differential potential of DPSCs may be regulated by MAO titanium surface.The osteogenesis potential of DPSCs on the MAO titanium was similar with BMSCs.展开更多
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
基金Supported by São Paulo Research Foundation(FAPESP),No.2010/08918-9 and 2020/11564-6the KBSP Young Investigator Fellowship,No.2011/00204-0+2 种基金the DBF Fellowship,No.2019/27492-7the LMG Fellowship,No.2014/01395-1the CFB Fellowship,No.2014/14278-3.
文摘BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
基金Supported by the Science and Technology Programme of Guangzhou City,No.202201020341.
文摘BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173 (both to ML)。
文摘Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.
基金Supported by Wuhan University of Science and Technology Startup Fund(Chu Tian Scholars Program),No.XZ2020024Open Laboratory Fund from Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration,No.2022kqhm005Hubei Provincial Health and Health Commission Research Project,No.WJ2023M121。
文摘Peripheral nerve injury(PNI)seriously affects people’s quality of life.Stem cell therapy is considered a promising new option for the clinical treatment of PNI.Dental stem cells,particularly dental pulp stem cells(DPSCs),are adult pluripotent stem cells derived from the neuroectoderm.DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages,such as easy isolation,multidifferentiation potential,low immunogenicity,and low transplant rejection rate.DPSCs are extensively used in tissue engineering and regenerative medicine,including for the treatment of sciatic nerve injury,facial nerve injury,spinal cord injury,and other neurodegenerative diseases.This article reviews research related to DPSCs and their advantages in treating PNI,aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.
基金supported by the Natural Science Foundation of China (81171470 and 81100761)the key clinical specialty discipline construction programme of Fujian, Chinathe Key Project of Science and Technology Bureau of Jiangsu Province (BL2013002)
文摘Postnatal mesenchymal stem cells have the capacity to differentiate into multiple cell lineages. This study explored the possibility of dental pulp stem cells (DPSCs) for potential application in tendon tissue engineering. The expression of tendon- related markers such as scleraxis, tenascin-C, tenomodulin, eye absent homologue 2, collagens I and VI was detected in dental pulp tissue. Interestingly, under mechanical stimulation, these tendon-related markers were significantly enhanced when DPSCs were seeded in aligned polyglycolic acid (PGA) fibre scaffolds. Furthermore, mature tendon-like tissue was formed after transplantation of DPSC-PGA constructs under mechanical loading conditions in a mouse model. This study demonstrates that DPSCs could be a ootential stem cell source for tissue enEineerin~ of tendon-like tissue.
基金the National Key R&D Program of China,No.2017YFA0104800the Project of Science&Technology Bureau of Chengdu,No.2016-HM01-00071-SFSichuan Academic&Technological Leaders Training Support Project.
文摘BACKGROUND Nerve diseases and injuries,which are usually accompanied by motor or sensory dysfunction and disorder,impose a heavy burden upon patients and greatly reduce their quality of life.Dental pulp stem cells(DPSCs),derived from the neural crest,have many characteristics that are similar to those of neural cells,indicating that they can be an ideal source for neural repair.AIM To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery.METHODS DPSCs were isolated,cultured,and identified by multilineage differentiation and flow cytometry.Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction.Then,we collected the secretions of DPSCs.We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays.Finally,we generated a sciatic nerve crush injury model in vivo and used the sciatic function index,walking track analysis,muscle weight,and hematoxylin&eosin(H&E)staining to further evaluate the nerve repair ability of DPSCs.RESULTS DPSCs highly expressed several specific neural markers,including GFAP,S100,Nestin,P75,and NF200,and were inclined toward neural differentiation.Furthermore,neural-induced DPSCs(N-DPSCs)could express neurotrophic factors,including NGF,BDNF,and GDNF.The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells.In vivo,both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy.However,in terms of anatomy and motor function,as shown by H&E staining,immunofluorescent staining,and walking track analyses,the repair effects of N-DPSCs were more sustained,potent,and effective than those of DPSCs and the controls.CONCLUSION In summary,this study demonstrated that DPSCs are inclined to differentiate into neural cells.N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs.Furthermore,our results suggested that NDPSCs could help crushed nerves with functional recovery and anatomical repair in vivo.Thus,DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.
基金Supported by National Natural Science Foundation of China,No.81800929 and No.81771033Sichuan Science and Technology Program,No.2019JDRC0096and Research and Develop Program,West China Hospital of Stomatology Sichuan University,No.LCYJ2019-24.
文摘Regenerative endodontics(RE)therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex.Current clinical RE procedures recruit endogenous stem cells from the apical papilla,periodontal tissue,bone marrow and peripheral blood,with or without application of scaffolds and growth factors in the root canal space,resulting in cementum-like and bone-like tissue formation.Without the involvement of dental pulp stem cells(DPSCs),it is unlikely that functional pulp regeneration can be achieved,even though acceptable repair can be acquired.DPSCs,due to their specific odontogenic potential,high proliferation,neurovascular property,and easy accessibility,are considered as the most eligible cell source for dentin–pulp regeneration.The regenerative potential of DPSCs has been demonstrated by recent clinical progress.DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp.The self-renewal,proliferation,and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors.Over recent decades,epigenetic modulations implicating histone modifications,DNA methylation,and noncoding(nc)RNAs have manifested as a new layer of gene regulation.These modulations exhibit a profound effect on the cellular activities of DPSCs.In this review,we offer an overview about epigenetic regulation of the fate of DPSCs;in particular,on the proliferation,odontogenic differentiation,angiogenesis,and neurogenesis.We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.
基金This study was supported by Yu Weihan Fund for Distinguished Young Scholars of Harbin Medical University of China,No.002000013(to XMZ).
文摘Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest.They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic factors.Few studies have reported Alzheimer’s disease treatment using dental pulp stem cells.Rat models of Alzheimer’s disease were established by injecting amyloid-β1–42 into the hippocampus.Fourteen days later,5×106 dental pulp stem cells were injected into the hippocampus.Immunohistochemistry and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin,NeuN,and neurofilament 200 in the hippocampus,while the expression of amyloid-βwas decreased.Moreover,cognitive and behavioral abilities were improved.These findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins,which indicates a potential therapeutic effect for Alzheimer’s disease.This study was approved by the Animal Ethics Committee of Harbin Medical University,China(approval No.KY2017-132)on February 21,2017.
基金funded by The Peabody Foundation Inc.,the Anthony and Constance Franchi Fund for Pediatric Orthopaedics at the Mass General Hospital for Children, and the National Natural Science Foundation of China (30801304)Foundation for the Author of National Excellent Doctoral Dissertation of PR China (FANEDD 200977)
文摘Aim The aim of this study was to confirm the multilineage differentiation ability of dental pulp stem cells (DPSCs) from green fluorescent protein (GFP) transgenic mice. The expression of GFP in DPSCs was also observed during differentiation. Methodology DPSCs were harvested from the dental pulp tissue of transgenic nude mice, and then transferred to osteogenic, adipogenic, and chondrogenic media. The morphological characterization of induced cells was observed by microscopy and histological staining. The expression of marker genes was measured by RT-PCR. Results The endogenous GFP and multilineage potential of transgenic DPSCs had no influence on each other. Moreover, the results of fluorescence microscopic imaging suggest that there was no significant decline of GFP expression during DPSCs differentiation. Conclusion As the population of GFP labeled DPSCs can be easily identified, this will be a promising method for tracking DPSCs in vivo.
基金supported by Yu Weihan Fund for Distinguished Young Scholars of Harbin Medical University of China,No. 002000013 (to XMZ)。
文摘Dental pulp stem cells are a type of adult stem cells with strong proliferative ability and multi-differentiation potential. There are no studies on treatment of vascular dementia with dental pulp stem cells. In the present study, rat models of vascular dementia were established by two-vessel occlusion, and 30 days later, rats were injected with 2 × 10^(7) dental pulp stem cells via the tail vein. At 70 days after vascular dementia induction, dental pulp stem cells had migrated to the brain tissue of rat vascular dementia models and differentiated into neuronlike cells. At the same time, doublecortin, neurofilament 200, and Neu N m RNA and protein expression levels in the brain tissue were increased, and glial fibrillary acidic protein m RNA and protein expression levels were decreased. Behavioral testing also revealed that dental pulp stem cell transplantation improved the cognitive function of rat vascular dementia models. These findings suggest that dental pulp stem cell transplantation is effective in treating vascular dementia possibly through a paracrine mechanism. The study was approved by the Animal Ethics Committee of Harbin Medical University(approval No. KY2017-132) in 2017.
基金funded by Egyptian Cultural and Educational Bureau in London,Egyptian mission sector and ministry of higher education in Egypt(grant No.GAM2649)。
文摘Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.
基金funded by the BBSRC(grant number BB/F017553/1the Rosetrees Trust
文摘Author contributions: Mead B was responsible for study conception and design, collection and^or assembly of data, data analysis and interpretation and manuscript writing. Logan A participated in study conception and design, data analysis and interpretation and manuscript writing. Berry M was responsible for manuscript writing. Scheven BA was in charge of study conception and design, data analysis and interpretation and manuscript writing. Leadbeater W participated in study conception and design, data analysis and interpretation and manuscript writing. All authors approved the final version of this paper.
基金Supported by National Natural Science Foundation of China,No. U21A20369Sichuan Science and Technology Program,No. 2021YJ0147Research and Develop Program,West China Hospital of Stomatology Sichuan University,No. RD-02-202113
文摘For more than 20 years,researchers have isolated and identified postnatal dental pulp stem cells(DPSCs)from different teeth,including natal teeth,exfoliated deciduous teeth,healthy teeth,and diseased teeth.Their mesenchymal stem cell(MSC)-like immunophenotypic characteristics,high proliferation rate,potential for multidirectional differentiation and biological features were demonstrated to be superior to those of bone marrow MSCs.In addition,several main application forms of DPSCs and their derivatives have been investigated,including stem cell injections,modified stem cells,stem cell sheets and stem cell spheroids.In vitro and in vivo administration of DPSCs and their derivatives exhibited beneficial effects in various disease models of different tissues and organs.Therefore,DPSCs and their derivatives are regarded as excellent candidates for stem cell-based tissue regeneration.In this review,we aim to provide an overview of the potential application of DPSCs and their derivatives in the field of regenerative medicine.We describe the similarities and differences of DPSCs isolated from donors of different ages and health conditions.The methodologies for therapeutic administration of DPSCs and their derivatives are introduced,including single injections and the transplantation of the cells with a support,as cell sheets,or as cell spheroids.We also summarize the underlying mechanisms of the regenerative potential of DPSCs.
基金supported by Science and Engineering Research Board,Government of India to AD(SB/YS/LS-122/2013)
文摘The hippocampal formation, important for spatial learn- ing and memory function, exhibits high level of plas- ticity in response to behavioral changes as well as injury. Dysfunction of the hippocampus is one of the hallmark features of neurodegenerative diseases like temporal lobe epilepsy (TLE) and Alzheimer's disease (AD) (Dhanush- kodi and Shetty 2008). Excitotoxicity is one of the known mechanisms by which neurons undergo degeneration in neurodegenerative condition (Haglid et al., 1994; Doble et al., 1995). Brain regions such as hippocampus are more susceptible to excitotoxic damage. During excitotoxicity.
文摘Objectives: The aim of this review is to explain the role of Dental Pulp Stem Cells (DPSCs) in repairing or regenerating damaged tissue/organs for both systemic and oral diseases and, in addition, review the differentiation, isolation of dental pulp stem cells and their applications in regenerative medicine. Materials and Methods: An electronic search was done using Cohchrane, PubMed and Google Scholar. Out of 310 articles, only 25 articles have been selected to be included in this review because it is directly related to the topic and they are matching the inclusion criteria of this review: “Language: English” and “Year: 2006-2016”. Results: DPSCs have been widely used as a mesenchymal stem cells source due to easy accessibility and less invasive harvesting. DPSCs could be used for pulpal regeneration, tooth reconstruction, endocrinology, neurology, angiogenesis and vasculogenises. The most common application of DPSCs in the dental field is pulp regeneration. Conclusion: Stem cell-based therapy holds a great promise to solve health problems from both systemic and oral diseases. Studying in DPSCs grows rapidly;however, there are still questionable issues needed to be optimized and answered such as the variable biological capacity of DPSCs.
基金the research grant No. 1.1266 from International Centre for Science, High Technology and Environmental Sciences
文摘Stem cells were isolated from human dental pulp using an optimized method, in which pulp pieces were digested by enzymes and immobilized to enhance cell outgrowth. Stem cell marker expression was detected by reverse transcription-PCR (RT-PCR), and differentiation markers were detected by real-time quantitative RT-PCR and immunocytochemistry. Results showed that dental pulp stem cells actively expressed nanog, oct4, nucleostemin slain-l, jmjdla, jmjd2c, and cyclin DI. When stem cells were induced to differentiate into neurons, nucleostemin, nanog, and cyclin D1 expression significantly decreased, whereas expression of neuronal markers, such as microtubule associated protein-2 and neurofilament-heavy, significantly increased. These results suggested that stem cells exited a pluripotent state and entered a neuronal differentiation pathway. In addition, results demonstrated that human dental pulp serves as a reservoir of stem cells that express defined stem cell markers; these cells were easily isolated and were induced to differentiate towards a desired cell lineage.
基金supported by the Innovation Fund of Huazhong University of Science and Technology,Wuhan,P.R. China (No.2011JC018)
文摘The presence of insufficient bone volume affects the implant healing and success.The aim of this study was to evaluate osteogenic capacity of dental pulp stem cells(DPSCs) on micro-arc oxidation(MAO) titanium surface.DPSCs were challenged at MAO and smooth titanium surface separately for different durations,and the bone marrow mesenchymal stem cells(BMSCs) served as the positive controls.The osteogenic capacity of DPSCs on MAO titanium surface was assessed by using scanning electron microscopy,energy dispersive spectroscopy,biochemical tests and real-time quantitative PCR.Data showed that DPSCs differentiated into osteoblasts and expressed bone morphogenetic genes on MAO titanium surface.The results of this study revealed that DPSCs had good potential to generate mineralized tissue on MAO titanium plates.The differential potential of DPSCs may be regulated by MAO titanium surface.The osteogenesis potential of DPSCs on the MAO titanium was similar with BMSCs.