牙髓干细胞修复周围神经损伤的研究进展

周围神经损伤(peripheral nerve injury,PNI)严重影响患者的生命质量及身心健康,并且损伤后的修复在临床上仍面临巨大挑战,PNI与再生修复研究是当今各相关学科研究的热点问题。细胞疗法在组织再生与修复中具有不可替代的作用。施万细胞是周围神经修复的理想细胞,但来源有限等缺点限制了其临床应用。牙髓干细胞来源于神经嵴,为神经再生提供了新的细胞来源。本文就牙髓干细胞修复PNI的研究现状进行综述。     

牙髓干细胞修复周围神经损伤的研究进展

周围神经损伤(peripheral nerve injury,PNI)严重影响患者的生命质量及身心健康,并且损伤后的修复在临床上仍面临巨大挑战,PNI与再生修复研究是当今各相关学科研究的热点问题。细胞疗法在组织再生与修复中具有不可替代的作用。施万细胞是周围神经修复的理想细胞,但来源有限等缺点限制了其临床应用。牙髓干细胞来源于神经嵴,为神经再生提供了新的细胞来源。本文就牙髓干细胞修复PNI的研究现状进行综述。     

Oct4调节成体干细胞多能性的研究进展

成体干细胞是存在于人和哺乳动物特定组织中的具有自我更新和一定分化潜能的未成熟细胞,参与成体组织的更新和创伤修复.牙髓干细胞是牙髓损伤修复的潜能所在,如何调控其生物学行为以促进牙髓修复再生是当前的研究热点.Oct4 在干细胞发育的基因调控网络中居核心地位,近年研究显示Oct4 具有维持成体干细胞多能性的功能.本文通过阐述Oct4 的结构和功能,揭示其在成体干细胞中的调节作用,为研究Oct4 对牙髓干细胞的调节作用提供理论基础.     

干细胞和支架与牙髓再生及其血运重建

在牙髓再生中,获取干细胞的方法包括干细胞移植、细胞归巢和诱导出血。干细胞移植可产生异位的牙髓样组织,可控制移植细胞的数量并选择对牙髓再生潜在效能最佳的细胞亚种。细胞归巢是指利用信号分子招募宿主内源性干细胞至需治疗的牙体根管中增殖和分化,形成牙髓-牙本质样组织。诱导根尖出血进入根管为年轻恒牙牙髓再生的一个重要步骤。支架是细胞在合成组织时的支撑结构,可促进细胞黏附,为牙髓再生提供有利的环境。牙髓再生离不开血运重建或者血管再生,感染控制、根管预处理、冠方封闭等操作,可为牙髓再生包括其血运重建提供适宜的环境。总之,组织工程技术在牙髓领域的应用发展为牙髓再生带来了新的希望。     

牙髓再生的临床应用与未来

旨在修复牙髓牙本质复合体的牙髓再生治疗是近年来的研究热点,目前仅有牙髓血运重建技术已实现临床初步应用,而干细胞移植和细胞归巢等技术尚处于临床前阶段。经过多年的基础研究和临床实践,牙髓再生特别是牙髓血运重建技术在取得进展的同时也暴露出不少问题,包括概念混淆、适应证选择不当、评价标准不完善等。为此,本综述从牙髓血运重建技术出发,对牙髓再生临床应用的现状、存在的问题和未来的临床实践路径等进行分析和探讨。     

牙髓干细胞与牙本质再生相关性的研究进展

牙髓中存在具备自我更新和多向分化潜能的牙髓干细胞。这些细胞经诱导可向成牙本质细胞分化并形成牙本质样结构，有望成为牙本质再生的种子细胞。本文就牙髓干细胞的来源、生物学特性及其在牙本质再生中的应用作一综述。     

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。     

牙髓干细胞分化的研究进展

牙髓干细胞(DPSC)是一种具有高度增生、自我更新能力和多相分化潜能的成体干细胞,在一定条件下可向特定的细胞类型分化,在牙髓修复和牙齿再生中发挥着重要的作用。本文主要就DPSC成骨向分化、成牙本质向分化的研究进展作一综述。     

基于外泌体的牙髓再生策略

近年来, 基于牙源性干细胞的牙髓再生研究已取得突破性进展, 部分研究结果已用于临床治疗。随着对牙髓再生机制的深入研究, 学者发现干细胞分泌的外泌体在其中扮演着重要角色。外泌体因其相较干细胞而言具有来源广泛、效果直接、免疫排斥反应小等优势, 有望通过募集宿主细胞的方式再生牙髓组织。本文将介绍牙髓再生和外泌体组织再生的研究现状, 结合牙髓组织再生特点和外泌体生物学特点, 对外泌体用于牙髓组织再生的相关研究进行分析和总结, 并探究外泌体用于牙髓组织再生的构建策略。     

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。     

Dental stem cells: Progress and perspectives

Dental pulp stem cells (DPSCs) are thought to contribute to reparative dentin formation, and that they may correspond to heterogenous populations of precursor cells or represent distinct differentiation stages along the odontoblastic lineage. DPSCs share many similarities with mesenchymal stem cells of the bone marrow (BMSCs). It appears that the distribution of tissue stem cells is not random and, within the dental pulp, there are potentially several distinct niches of stem/progenitor cells. In addition to DPSCs, other dental stem cell populations have been isolated. As for DPSCs, further studies are still needed to evaluate their potential of differentiation and their regenerative activity. Up today, (1) the formal demonstration that pulpal resident stem cells are actually the reparative dentin-forming cells recruited in response to injury is still lacking; and (2) the origin, localization and precise identity of odontogenic stem cells remain largely unknown. Dental clonal cell lines may represent valuable tool to answer some fontamental questions concerning the dental stem cell biology. Altogether, the presence of dental cell populations displaying stem cell properties has opened new paths for considering regenerative therapies. This might be a prerequisite to design alternative strategies for capping and endodontic treatment, using stem cells.     

Stand der humanen dentalen Stammzellforschung

This review article arranges the current results of stem cell biology for their use in dentistry. There are different types of stem cells, which are applicable for dental treatments. The use of embryonic stem cells, whose possibilities for breeding an artificial tooth were hardly evaluated, is however ethically precarious. On the other side the ethically harmless adult stem cells, which were isolated for example from bone marrow, were little examined for their capability of differentiation into dental tissues. Therefore their forthcoming use in dentistry is rather improbable. However, dental ectomesenchymal stem cells are more promising for dentistry in future. For example dental pulp stem cells (DPSCs) are capable to differentiate into dentin under in vitro conditions. Moreover it is possible to use periodontal ligament (PDL) stem cells and dental follicle precursors for periodontal tissue differentiations in vitro. Recently new populations of stem cells were isolated from the dental pulp and the PDL. These cells distinguish from the initially isolated DPSCs and PDL stem cells in growth and cell differentiation. Therefore stem cell markers are very important for the characterization of dental stem cells. A significant marker for dental stem cells is STRO-1, which is also a marker for bone marrow derived mesenchymal stem cells. Nonetheless dental stem cells are CD45 negative and they express rarely hematopoietic stem cell markers. These research results plead for the participation of dental stem cells in dental practice in future.     

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.     

牙髓干细胞分化过程中L型钙离子通道羧基末端的表达

目的:探讨牙髓干细胞(DPSCs)分化过程中L型钙离子通道羧基末端的表达。方法:利用酶消化法体外分离、培养大鼠牙髓干细胞;吉姆萨染色法检测大鼠牙髓干细胞的克隆形成能力;神经诱导体系下诱导牙髓干细胞向神经样细胞分化,免疫荧光染色检测细胞分化后胶质纤维酸蛋白(glial fibrillary acidic pro-tein,GFAP)的表达和细胞分化前后L型钙离子通道Cav 1.2及羧基末端的表达。结果:牙髓干细胞的克隆形成能力为每1 000个细胞形成2～17个克隆;免疫荧光染色检测诱导后细胞GFAP表达阳性;免疫荧光染色检测显示:牙髓干细胞分化前L型钙离子通道Cav 1.2羧基末端表达于细胞膜上,细胞分化后羧基末端同时表达于细胞膜上和细胞核中。结论:L型钙离子通道Cav 1.2羧基末端在牙髓干细胞分化过程中发生核转位,羧基末端可能在牙髓干细胞的分化过程中发挥着一定的作用。     

牙髓干细胞在周围神经损伤修复中的研究进展

周围神经损伤(peripheral nerves injury,PNI)是口腔临床常见病,极易造成患者功能丧失和美观异常,牙髓干细胞(dental pulp stem cells,DPSCs)结合组织工程在PNI修复中的应用是目前研究热点.DPSCs具有来源丰富、提取简单、免疫原性低以及体外增殖率高等优点,其可分化成雪...     

Notch配体Delta-1对人牙髓干细胞体外增殖的影响

目的:探讨Notch配体Delta-1对人牙髓干细胞(dentalpulpstemcells,DPSCs)体外增殖活性的影响。方法:用Delta-1-EGFP重组逆转录病毒感染培养的人牙髓干细胞,获得稳定高表达人Delta-1蛋白的人牙髓干细胞系;利用CFU-F计数、四唑盐(MTT)比色法及流式细胞仪等方法检测Delta-1基因转导人牙髓干细胞的克隆形成率、细胞生长曲线和细胞周期变化。结果:与正常牙髓干细胞相比,Delta-1转导人牙髓干细胞的CFU-F计数为62～89clones/103cell,约为前者的10倍;接种1～7d,转导细胞的活细胞数量增加显著;S期细胞比例及增殖指数,分别从转导前的20.6%和35.8%提高到63.8%和75.7%。结论:Notch配体Delta-1可显著促进人牙髓干细胞的体外增殖,Notch-Delta-1信号转导途径在人牙髓干细胞的自我更新中起重要作用。     

牙髓培养细胞特性与牙髓干细胞定位

目的 比较人牙根髓与冠髓培养细胞的特性，探讨牙髓干细胞在牙髓中的定位。方法：用组织块法分别培养人根髓、冠髓细胞，观察并比较两者的培养成功率、细胞贴壁率、细胞活性、增殖特性、细胞形态以及细胞诱导矿化能力，以探讨牙髓干细胞在牙髓组织中的定位。结果：培养的根髓细胞比冠髓细胞具有较高的成功率和贴壁率、较强的细胞活性以及相同的增殖活性，根髓细胞比冠髓细胞的形态更具有原始性，根髓比冠髓更易诱导矿化。结论：牙髓干细胞可能存在于全部牙髓之中，在根髓中比冠髓中具有更高的密度．     

Dental pulp stem cells: State of the art and suggestions for a true translation of research into therapy

ObjectivesStem cells have the ability to rescue and/or repair injured tissue. In humans, it is possible to isolate different types of stem cells from the body. Among these, dental pulp stem cells (DPSCs) are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. In particular they represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies.SourcesAn electronic search was conducted on PubMed databases and supplemented with a manual study of relevant references.ResultsAll research described in this review highlight that DPSCs are mesenchymal stem cells that could be used in clinical applications. Unfortunately, very few clinical trials have been reported. Major obstacles imposed on researchers are hindering the translation of potentially effective therapies to the clinic. Both researchers and regulatory institutions need to develop a new approach to this problem, drawing up a new policy for good manufacturing practice (GMP) procedures. We strongly suggest that only general rules be standardized rather than everything. Importantly, this would not have an effect on the safety of patients, but may very well affect the results, which cannot be identical for all patients, due to physiological diversity in the biology of each patient. Alternatively, it would be important to study the role of specific molecules that recruit endogenous stem cells for tissue regeneration. In this way, the clinical use of stem cells could be successfully developed.ConclusionsDPSCs are mesenchymal stem cells that differentiate into different tissues, maintain their characteristics after cryopreservation, differentiate into bone-like tissues when loaded on scaffolds in animal models, and regenerate bone in human grafts. In summary, all data reported up to now should encourage the development of clinical procedures using DPSCs.     

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。