牙髓干细胞的研究

牙髓干细胞是存在于牙髓组织中的一种成体干细胞，具有高度增殖、自我更新的能力和多向分化的潜能。牙髓干细胞的研究对牙组织工程和牙齿的再生将产生重要的意义。本文就牙髓干细胞的研究现状作一综述，并对其应用前景以及目前存在的问题进行讨论。     

牙髓干细胞的研究进展

牙髓干细胞是牙髓组织中具有高度增殖、自我更新的能力并可多向分化的一类成体干细胞,在牙髓修复和牙齿再生以及骨组织工程相关研究中发挥重要作用。本文就牙髓干细胞的研究现状作一综述,并讨论其应用前景以及目前存在的问题。     

牙髓干细胞的研究与应用

牙髓干细胞（dental pulp stem cells,DPSCs）是牙髓组织中高度增殖、具有自我更新能力和多向分化潜能的一类成体干细胞,在牙齿、骨和神经的修复、再生以及组织工程相关研究中具有重要作用。本文主要从 DPSCs 的生物学特性、分化潜能以及组织工程应用等方面综合分析了 DPSCs 研究的进展。     

牙髓干细胞研究进展

干细胞是一类具有自我更新和分化潜能的细胞，它包括胚胎干细胞和成体干细胞。牙髓干细胞具有成体干细胞所界定的两大特征：较强的自我更新能力和分化潜能。牙髓干细胞因具有临床取材容易并可特异性地分化为牙体矿化结构等特性，目前正受到广泛关注。     

牙髓干细胞在组织工程领域的研究进展

种子细胞的获得、培养与分化是组织工程的前提和基础,将干细胞作为种子细胞用于组织工程的构建受到越来越多学者的关注。牙髓干细胞（DPSCs）是存在于牙髓组织中的一种成体干细胞,是一种新兴的组织工程种子细胞,对于组织器官的再生具有重要的意义。本文就牙髓干细胞在组织工程的研究现状作一综述,并对其临床应用前景进行讨论。     

成体干细胞在组织工程化牙本质牙髓复合体中的应用研究与展望

牙髓干细胞(dental pucp stem cells，DPSCs)是一种成体干细胞。有关成体十细胞的研究进展，尤其是骨髓基质干细胞(bone marrow stromal stem cells，BMSSCs)的研究，为牙髓干细胞的研究提供了可以借鉴的思路和方法。DPSCs也有相对特异的识别途径和特点，其中重要的特征之一是一定条件下能形成牙本质牙髓复合体。这将为其应用于组织工程中重建牙本质牙髓复合体，展示了巨大的优越性和可行性，也为其在牙髓生理、病理、牙髓病的生物治疗方面的研究提供了重要的应用价值。     

牙髓干细胞及其表面特异标志物

牙髓干细胞是位于牙髓组织中的一种成体干细胞,具有高度增殖与多向分化的能力。牙髓干细胞的出现,为牙髓病的治疗提供了新的治疗途径。下面就牙髓干细胞及其表面特异性标志物的研究进展作一综述。     

人牙髓细胞的体外培养

对牙髓细胞的体外培养是研究牙髓的有效工具。随着细胞培养技术的发展,牙髓细胞培养的成功率不断提高。干细胞生物学的研究使得人们认识到,在成体组织中也存在干细胞。目前不仅已分离出牙髓干细胞,而且对其干细胞特征作了进一步的研究,这将给牙髓病治疗和牙齿组织工程带来重大的变化。     

牙髓中的干细胞

和体内其它组织一样，牙髓中也存在成体干细胞－牙髓干细胞，它有分化为其它细胞的能力。但对其定性和定位尚不明确。该细胞不表达牙本质唾磷蛋白，碱性磷酸酶活性也较低。免疫组化研究表明，牙髓干细胞和骨髓间充质干细胞有施工相似之处，但也有细胞特异性的表面标记物。关于它的研究对于牙髓生理学，根管治疗学等产生深远的影响。     

牙髓中的干细胞

和体内其它组织一样,牙髓中也存在成体干细胞——牙髓干细胞,它有分化为其它细胞的能力。但对其定性和定位尚不明确。该细胞不表达牙本质唾磷蛋白,碱性磷酸酶活性也较低。免疫组化研究表明,牙髓干细胞和骨髓间充质干细胞有许多相似之处,但也有细胞特异性的表面标记物。关于它的研究将对牙髓生理学、根管治疗学等产生深远的影响。     

牙源性干细胞及牙髓再生的研究进展

牙髓组织中含有细胞、血管、神经和纤维等,是一个复杂的3D结构系统。随着干细胞生物学和组织工程学的相互结合和促进,牙髓再生逐渐成为可能。牙体组织中分离出的多种干细胞,如牙髓干细胞、脱落乳牙牙髓干细胞、根尖牙乳头干细胞、牙囊干细胞等,都具有再生牙髓的潜能。文章就牙源性干细胞及以牙源性干细胞为基础的牙髓再生的研究进展做一综述。     

牙源性间充质干细胞诱导iPS细胞的效率与时间的研究

目的研究比较不同种牙源性间充质干细胞诱导iPS细胞的效率与时间。方法分离牙髓干细胞（DPSCs）、脱落乳牙干细胞（SHED）、牙乳头干细胞（SCAP）。应用慢病毒介导Lin28、Nanog、Oct4和Sox2因子重编程获得iPS细胞。比较在同等条件下三种细胞获得iPS细胞的克隆数与平均诱导时间。结果DPSC诱导iPS细胞的效率是0.167%,高于SHED细胞和SCAP细胞的诱导效率（0.125%,0.033%）;DPSC诱导iPS细胞的平均重编程时间是20.1d,均少于SHED细胞和SCAP细胞（23.73d,25.25d）,差异均有统计学意义。结论三种不同牙源性细胞有不同的iPS细胞诱导效率与重编程时间,牙髓干细胞有较好的诱导iPS细胞的应用潜能。     

Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells

ObjectiveThis study focused on the characterization of stem cells from human exfoliated deciduous teeth (SHED) in comparison with dental pulp stem cells (DPSCs) to certify SHED as a key element in tissue engineering.MethodsIn the present study, SHED and DPSCs were assayed for their cell surface antigens and proliferation by measuring the cell cycles, growth rates, Ki67-positive efficiencies, and colony-forming units (CFUs). The evaluation of multi-differentiation was performed using alizarin red and oil red O and real-time PCR in vitro. The mineralization capability of the cells was examined in vivo by implanting with ceramic bovine bone (CBB) into subcutaneous of immunocompromised mice for 8 weeks. A three-dimensional pellet cultivation system is proposed for SHED and DPSCs to recreate the biological microenvironment that is similar to that of a regenerative milieu.ResultsSHED showed a higher proliferation rate and differentiation capability in comparison with DPSCs in vitro, and the results of the in vivo transplantation suggest that SHED have a higher capability of mineralization than the DPSCs. The mRNA expression levels of inflammatory cytokines, including matrix metalloproteinase-1 (MMP1), tissue inhibitors of metalloproteinase-1 (TIMP1), matrix metalloproteinase-2 (MMP2), tissue inhibitors of metalloproteinase-2 (TIMP2) and interleukin-6 (IL-6) were higher in SHED than that in DPSCs. In addition, the expression levels of Col I and proliferating cell nuclear antigen (PCNA) in SHED sheets were significantly higher than those in DPSCs sheets.ConclusionsThis study systematically demonstrated the differences in the growth and differentiation characteristics between SHED and DPSCs. Consequently, SHED may represent a suitable, accessible and potential alternative source for regenerative medicine and therapeutic applications.     

人乳牙牙髓干细胞在干细胞治疗中的应用

乳牙牙髓干细胞（SHED）是牙源性干细胞的一种,属外胚间充质干细胞。作为一种理想的干细胞来源,SHED在干细胞治疗中有良好的应用前景。本文阐述了SHED的生物学特征及其在干细胞治疗中的优势,探讨了SHED在组织再生和修复中发挥的多向分化潜能、细胞分泌功能和免疫调节功能等方面的功能作用。此外,本文还介绍了SHED在各系统、器官疾病治疗中的临床应用,重点阐述了用SHED进行干细胞移植在牙髓—牙本质再生、颌骨再生、神经系统疾病治疗和免疫系统疾病治疗方面的研究进展。     

人乳牙牙髓干细胞和恒牙牙髓干细胞的蛋白质组学比较

目的 采用蛋白质组学方法研究人乳牙牙髓干细胞（SHED）和恒牙牙髓干细胞（DPSC）中的蛋白表达差异.方法 应用双向凝胶电泳技术分离SHED和DPSC的细胞总蛋白.通过比较两种细胞的蛋白组学图谱,确定差异表达的蛋白点,而后对差异点进行基质辅助激光解析电离飞行时间质谱分析和蛋白数据库信息检索,对差异蛋白进行功能分类.结果 建立了SHED和DPSC的蛋白质组图谱,经软件分析出45个差异蛋白点,其中26个表达上调,19个表达下调,再经质谱鉴定出48种蛋白,其生物学功能涉及细胞周期、代谢等.结论 SHED与DPSC中蛋白的差异表达体现了两种细胞在结构和功能上的异同性,为进一步研究SHED和DPSC在增殖、分化中的差异,以及牙齿相关干细胞在组织工程和再生医学研究中的应用提供参考.     

Stem Cell Proliferation Pathways Comparison between Human Exfoliated Deciduous Teeth and Dental Pulp Stem Cells by Gene Expression Profile from Promising Dental Pulp

IntroductionMesenchymal stem cells (MSCs) have been used for clinical application in tissue engineering and regenerative medicine (TERM). To date, the most common source of MSCs has been bone marrow. However, the bone marrow aspirate is an invasive and painful procedure for the donor. Thus, the identification and characterization of alternative sources of MSCs are of great importance. This study focused on the characterization of stem cells from human exfoliated deciduous teeth (SHED) compared with dental pulp stem cells (DPSCs) and bone marrow–derived mesenchymal stem cells (BMMSCs).MethodsWe have compared “stemness” such as the proliferation rate and the expression of stem cell marker of DPSCs, SHED, and BMMSCs. In addition, gene expression profile of DPSCs and SHED were analyzed by using DNA microarray.ResultsAll cells isolated from the three sources exhibited MSC characteristics including a fibroblastic morphology, and the expression of mesenchymal stem-cell markers. The proliferation rate of SHED was significantly higher than that of DPSCs and BMMSCs (P < 0.05). The comparison of the gene expression profiles indicated 4386 genes with a changed expression between DPSCs and SHED by 2.0-fold or more. Higher expression in SHED was observed for genes that participate in pathways related to cell proliferation and extracellular matrix, including several cytokines such as fibroblast growth factor and tumor growth factor beta.ConclusionsBecause of its advantages of a higher proliferation capability, abundant cell supply, and painless stem cell collection with minimal invasion, SHED could be a desirable option as a cell source for potential therapeutic applications.     

人恒牙牙髓干细胞体外定向诱导分化为成骨细胞的研究

目的:研究人恒牙牙髓组织来源的牙髓干细胞在体外分化为成骨细胞的能力,探讨其作为骨组织工程种子细胞的可行性.方法:从正畸治疗减数拔除的恒前磨牙中分离牙髓组织,应用酶消化法获得牙髓细胞.单抗Stro-1标记、免疫磁珠阳性分选系统分选获得牙髓干细胞,第3代牙髓干细胞用成骨向诱导培养基向成骨细胞诱导分化.用碱性磷酸酶染色和Vo...     

Stem cell‐based tooth and periodontal regeneration

Currently regeneration of tooth and periodontal damage still remains great challenge. Stem cell‐based tissue engineering raised novel therapeutic strategies for tooth and periodontal repair. Stem cells for tooth and periodontal regeneration include dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), stem cells from the dental apical papilla (SCAPs), and stem cells from human exfoliated deciduous teeth (SHEDs), dental follicle stem cells (DFSCs), dental epithelial stem cells (DESCs), bone marrow mesenchymal stem cells (BMMSCs), adipose‐derived stem cells (ADSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). To date, substantial advances have been made in stem cell‐based tooth and periodontal regeneration, including dentin–pulp, whole tooth, bioroot and periodontal regeneration. Translational investigations have been performed such as dental stem cell banking and clinical trials. In this review, we present strategies for stem cell‐based tissue engineering for tooth and periodontal repair, and the translational studies.     

Differentiation of stem cells from human deciduous and permanent teeth into spiral ganglion neuron-like cells

ObjectiveStem cells from pulp tissue are a promising cell-based therapy for neurodegenerative patients based on their origin in the neural crest. The aim of this study was to differentiate and evaluate the ability of human dental pulp stem cells from permanent teeth (DPSC) and stem cells from human exfoliated deciduous teeth (SHED) to differentiate into spiral ganglion neurons.DesignAfter isolation and characterization of mesenchymal stem cell properties, DPSC and SHED were treated with the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial cell-derived neurotrophic factor (GDNF). The differentiation was identified by immunostaining and qRT-PCR analysis of neuronal markers and measuring intracellular calcium activity.ResultsAfter 2 weeks of induction, morphological changes were observed in both DPSC and SHED. The differentiated cells expressed neuron-specific class III beta-tubulin, GATA binding protein 3 (GATA3) and tropomyosin receptor kinase B, protein markers of spiral ganglion neurons. These cells also showed upregulation of the genes encoding these proteins, namely GATA3 and neurotrophic receptor tyrosine kinase 2. Intracellular calcium dynamics that reflect neurotransmitter release were observed in differentiated DPSC and SHED.ConclusionThese results demonstrate that dental pulp stem cells from permanent and deciduous teeth can differentiate into spiral ganglion neuron-like cells.