椎间盘退变模型研究现状与进展

椎间盘退变疾病越来越被大家所重视,但退变的生物学机制尚不明确,构建椎间盘退变模型是研究的基础和关键.近年来国内外报道的新型椎间盘模型分为动物体外模型和动物体内模型两大类.动物体外模型包括椎间盘细胞模型和椎间盘组织块模型;动物体内模型有机械力学模型和外伤模型等.该文就近年来新型椎间盘退变模型的研究现状与进展作一综述.     

椎间盘退变模型研究进展

椎间盘退变的生物学机制尚不明确,构建椎闯盘退变模型是研究基础和关键.近年来国内外报道的新型椎间盘退变模型分为体外和体内培养模型两大类.体外模型包括椎间盘细胞模型和椎间盘组织块模型,多用于细胞生物学行为方面的研究,适用面较广,但培养要求较高,模拟体内环境有局限.体内模型有机械力学模型、外伤模型、酶化学模型、缺血模型、吸烟模型等,多用于采取特定干预措施的椎间盘退变模型的研究,适用面较窄,但干预技术较易实现.该文就近年来新型椎间盘退变模型的研究进展及各种模型的优缺点作一综述.     

椎间盘退变基因治疗进展

椎间盘退变是导致腰背痛的病理生理学原因之一。多年来,对椎间盘细胞、生化特性以及微环境的研究,发现椎间盘退变时呈现细胞凋亡、细胞数减少、重要的细胞外基质蛋白多糖和Ⅱ型胶原降低和基质金属蛋白酶活性增加等。因此,20世纪90年代后期许多学者开始研究新的治疗方法,即椎间盘退变的生物学治疗。生物学治疗包括细胞治疗、基因     

骨髓间充质干细胞治疗椎间盘退行性病变的研究进展

骨髓间充质干细胞(BMSCs)是一种良好的种子细胞,广泛用于椎间盘组织工程研究.椎间盘退变机制、BMSCs的生物学特性、支架材料及细胞因子认识的深入,为BMSCs应用于退变的椎间盘组织的修复奠定了一定基础.但是组织工程学应用BMSCs治疗椎间盘退行性病变还处于研究的初期阶段,目前仍存在很多问题,其中最为突出的是移植细胞存活问题.笔者就BMSCs治疗椎间盘退行性病变的相关研究作一综述.     

椎间盘退变模型研究进展

椎间盘退变的生物学机制尚不明确,构建椎间盘退变模型是研究基础和关键。近年来国内外报道的新型椎间盘退变模型分为体外和体内培养模型两大类。体外模型包括椎间盘细胞模型和椎间盘组织块模型,多用于细胞生物学行为方面的研究,适用面较广,但培养要求较高,模拟体内环境有局限。体内模型有机械力学模型、外伤模型、酶化学模型、缺血模型、吸烟模型等,多用于采取特定干预措施的椎间盘退变模型的研究,适用面较窄,但干预技术较易实现。该文就近年来新型椎间盘退变模型的研究进展及各种模型的优缺点作一综述。     

椎间盘退变分子机制与富血小板血浆修复作用的研究现状

目的综述椎间盘退变分子机制与富血小板血浆(platelet-rich plasma,PRP)修复作用的研究现状。方法查阅椎间盘退变分子机制与PRP修复作用的相关文献,并进行总结分析。结果椎间盘退变分子机制涉及基因影响、细胞衰老、细胞外基质改变、降解酶生成增加、促炎因子表达、细胞凋亡、神经内生长等方面。PRP能释放多种生长因子,促进椎间盘细胞增殖分化和细胞外基质合成、抑制炎性反应和细胞凋亡。结论 PRP在修复椎间盘退变的应用前景令人鼓舞,但仍需进一步深入研究。     

椎间盘退变生物学治疗研究进展

椎间盘退变主要表现为椎间盘内细胞数量减少和功能降低,以及蛋白聚糖和主要胶原成分进行性减少.生物学治疗包括细胞移植、组织工程、椎间盘内细胞因子注射和基因治疗,主要目标是恢复椎间盘的正常生理功能.细胞移植通过增加椎间盘中细胞的绝对数量使细胞外基合成增加,从而修复退变的椎间盘.组织工程通过体外构建完整的椎间盘组织,回植替代原有退变的椎间盘,以达到治疗目的.椎间盘内注射生长因子,能够有效地增加细胞的生物合成,但效应期较短.基因治疗则是将适当的调节基因导入椎间盘细胞,对椎间盘基质代谢可起到长效的调节作用.该文就生物学治疗椎间盘退变技术的原理、目前应用情况及今后发展动态作一综述.     

椎间盘退变中影响Sox9基因的相关因素

随着分子生物学的发展和对椎间盘退变的生物学机制的深入研究,人们已经越来越不满足于传统的椎间盘退变治疗方法,如卧床休息、理疗、药物治疗和手术治疗等.这些传统方法仅能短期缓解椎间盘退变给患者带来的痛苦,并不能从根本上终止退变进程.     

椎间盘退变病因和生物学治疗研究进展

椎间盘退变引起的下腰痛是骨科治疗的难点.研究发现过度压力导致终板微骨折,椎间盘细胞基因异常表达,椎间盘内基质内基质金属蛋白酶及其抑制因子比例失衡,炎症因子调节其他因子的异常表达及椎间盘细胞凋亡等均可造成椎间盘基质主要成分合成与分解失衡,诱导椎间盘退变;遗传多态性、年龄等也与之关系密切.椎间盘退变的治疗一直是下腰痛治疗研究的重点,近年来发展的基因治疗、细胞或髓核移植及组织工程等生物学治疗方法,从椎间盘退变的病因或发病途径着手,为根治椎间盘退变性疾病提供了希望.该文就椎间盘退变病因及生物学治疗的最新研究进展作一综述.     

椎间盘退变基因治疗的研究进展

椎间盘退变是成人下腰痛的主要原因之一,保守治疗和手术治疗常常不能取得满意的疗效。椎间盘退变分子病理机制涉及多种分子水平上的改变,相关的生物治疗研究亦越来越受到重视。目前生物治疗的材料包括细胞因子、基因以及细胞,分别对应细胞因子治疗、基因治疗以及组织工程。其中基因治疗又分为直接基因治疗和间接基因治疗。本综术主要围绕基因治疗靶点和各种基因载体来探讨基因治疗在椎间盘退变相关研究中的应用进展。     

细胞衰老及衰老相关分泌表型在椎间盘退变中的研究进展

椎间盘细胞在不断分裂增殖和外界不利因素的持续刺激下极易发生老化。衰老细胞在影响椎间盘结构和功能同时异常表达衰老相关分泌表型(SASP),通过分泌促炎因子、趋化因子、生长因子和蛋白酶类等物质加速椎间盘退变的进程。目前已证实抗衰老治疗在椎间盘退变疾病中有很好的应用前景,包括减少衰老细胞发生、细胞移植抗衰老治疗等,特别是近些年靶向干预SASP抗衰老治疗受到学者广泛关注。本文就近年来细胞衰老和SASP在椎间盘微环境中的作用机制及相关干预措施进行综述。     

Regeneration potential and mechanism of bone marrow mesenchymal stem cell transplantation for treating intervertebral disc degeneration

Intervertebral disc degeneration is a primary cause of low back pain and has a high societal cost. The pathological mechanism by which the intervertebral disc degenerates is largely unknown. Cell-based therapy especially using bone marrow mesenchymal stem cells as seeds for transplantation, although still in its infancy, is proving to be a promising, realistic approach to intervertebral disc regeneration. This article reviews current advances regarding regeneration potential in both the in vivo and vitro studies of bone marrow mesenchymal stem cell-based therapy and discusses the up-to-date regeneration mechanisms of stem cell transplantation for treating intervertebral disc degeneration.     

Future perspectives of cell-based therapy for intervertebral disc disease

Intervertebral disc degeneration is a primary cause of low back pain and has a high societal cost. Research on cell-based therapies for intervertebral disc disease is emerging, along with the interest in biological therapy to treat disc disease without reducing the mobility of the spinal motion segment. Results from animal models have shown promising results under limited conditions; however, future studies are needed to optimise efficacy, methodology, and safety. To advance research on cell-based therapy for intervertebral disc disease, a better understanding of the phenotype and differentiation of disc cells and of their microenvironment is essential. This article reviews current concepts in cell-based therapy for intervertebral disc disease, with updates on potential cell sources tested primarily using animal models, and discusses the hurdles to clinical application. Future perspectives for cell-based therapies for intervertebral disc disease are also discussed.

     

骨髓基质细胞在椎间盘退变中的应用

骨髓基质细胞具有很强的自我更新和多向分化潜能,在不同体外环境下,可诱导多胚层来源的细胞,如:骨细胞、软骨细胞、神经细胞等。椎间盘退变是脊柱退行性疾病及继发病变的基础,临床上十分多见,目前的治疗方法虽然很多,但均不是真正针对椎间盘退变的病理生理过程。骨髓基质细胞的细胞治疗和基因治疗作为椎间盘退变治疗的一种新方法,从根本上阻止和逆转椎间盘退变,必将成为治疗椎间盘退变的最佳途径。     

椎间盘退变生物学治疗的研究进展

椎间盘退变所致的颈肩腰腿痛严重影响许多患者的生活及工作,目前的治疗方法主要侧重于缓解疼痛症状或神经受压症状,而无法阻止椎间盘退变的进程,导致疾病具有高复发率。近年来学者们开始广泛研究椎间盘退变的生物学治疗方法,即通过生物分子治疗、基因治疗、细胞治疗和组织工程等方法来修复和重塑椎间盘,以期从根本上解决椎间盘退变的问题,而上述方法大多处于动物实验或体外实验阶段,临床应用尚存在诸多挑战。     

Micro-RNA与椎间盘退行性变的研究进展

下腰疼痛正在成为目前影响人们生活质量的重要因素,其发病的年龄越来越趋于年轻化,每年因下腰痛带来的社会经济损失巨大。椎间盘退变(intervertebral disc degeneration,IDD)是引起下腰疼的重要原因,在多重因素作用下,椎间盘组织出现生物力学和结构的变化,发生纤维环破裂、髓核组织突出,使脊髓和神经根受压,从而引起患者出现下腰疼。微小RNA(Micro-RNA,miRNA)是一类长度为18~24个核苷酸序列的单链非编码小分子RNA,其在真核生物中广泛存在,作为基因表达的重要调控分子之一,已被证明在许多种疾病起始及进展阶段发挥着关键作用,故认为其可能在椎间盘退变中也发挥着重要的作用。目前,临床上针对IDD的治疗手段主要以手术治疗缓解临床症状为主,即使当前手术治疗可以取得良好的疗效,但是手术治疗会给患者带来更大的身体创伤和经济负担。miRNA在椎间盘退变过程中的作用是当前学术界研究的热点之一,研究表明miRNA在退变的椎间盘组织中呈现异常的表达模式,参与IDD的多种病理过程。目前,一些miRNA已被证明与椎间盘退变过程中的多种病理过程有关,包括髓核细胞凋亡和增殖、细胞外基质的降解、细胞自噬、炎症反应及软骨终板的退变等。基因芯片对比研究显示一些miRNA在退变髓核细胞中的表达与正常髓核细胞存在明显差异,这些差异表达的miRNA通过调控其各自的上、下游通路可能参与髓核细胞退变的进程,调控通路多有交叉并行,构建出一个庞大的miRNA调控网。了解miRNA在发病过程中的靶基因和机制,能够在疾病的起源、发展和预后等方面提供重要参考。因此,综述了miRNA在椎间盘退变过程中的重要作用和潜在的临床治疗意义。随着对miRNA研究的深入,通过了解椎间盘退变的分子生物学机制,可以为IDD的诊断和治疗提供新思路,非常有可能成为IDD生物学治疗的新策略。     

Biologic modification of animal models of intervertebral disc degeneration

Intervertebral disc degeneration is a chronic process that can become manifest in clinical disorders such as idiopathic low back pain, sciatica, disc herniation, spinal stenosis, and myelopathy. The limited available treatment options (including discectomy and spinal fusion) for these and other disabling conditions that arise from intervertebral disc degeneration are highly invasive, achieve limited success, and only address acute symptoms while doing nothing to halt the process of degeneration. Although the precise pathophysiology of intervertebral disc degeneration has yet to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. Animal models as well as in vitro studies of the process of disc degeneration have yielded many potentially useful targets for the reversal of disc degeneration. One current research trend is the use of established animal models of disc degeneration to study the role of therapeutic modalities in reversing the process of degeneration, often with use of the delivery of genes or gene products that influence the anabolic and catabolic pathways of the disc. This article reviews the ability of gene-product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and examines future trends in this field.     

Articular cartilage and intervertebral disc proteoglycans differ in structure: an electron microscopic study

Articular cartilage and the intervertebral disc tissues have different material and biological properties and different patterns of aging and degeneration. To determine if the proteoglycans of these tissues differ in structure, we used the electron microscopic monolayer technique to compare baboon articular cartilage proteoglycans with baboon annulus fibrosus, transition zone, and nucleus pulposus proteoglycans. Intervertebral disc and articular cartilage proteoglycans differed significantly. Articular cartilage contained large proteoglycan aggregates formed from hyaluronic acid central filaments, multiple monomers, and large nonaggregated monomers. These molecules were identical to those of nasal cartilage, growth plate cartilage, chondrosarcomas, or menisci. In contrast, the intervertebral disc tissues contained only nonaggregated proteoglycan monomers and clusters of monomers without apparent central filaments. Intervertebral disc nonaggregated monomers were shorter and more variable in length than those from articular cartilage, and nucleus pulposus nonaggregated monomers were even shorter and more variable in length than transition zone and annulus fibrosus monomers. These observations suggest that significant differences in proteoglycan metabolism exist between articular cartilage and intervertebral disc.     

Cyclic mechanical stretch stress increases the growth rate and collagen synthesis of nucleus pulposus cells in vitro

STUDY DESIGN: A rabbit model designed to investigate the effects of applied cyclic tensile stress on the cell division rate and the collagen synthesis in the rabbit nucleus pulposus cells in vitro. OBJECTIVE: To evaluate the effects of mechanical stress on nucleus pulposus cells, thus adding to the understanding of the adaptation of the intervertebral disc to mechanical stress. SUMMARY OF BACKGROUND DATA: Intervertebral disc cells in vivo are exposed to a multitude of physical forces during physical motion. Although it is known that in intervertebral disc disease, a common pathway of disc degeneration is mechanical stress on the nucleus pulposus or the anulus fibrosus or both, the underlying mechanism has been less well defined. METHODS: Nucleus pulposus cells were isolated from 4-week-old Japanese white rabbits. These cells were subjected to the mechanical cyclic stretch stress using a computerized, pressure-operated instrument that physically deformed the cells. The DNA synthesis rate, collagen synthesis rate, and cell cycle progression were measured. RESULTS: Cyclic tensile stretch increased the DNA synthesis rate in nucleus pulposus cells and in the population of cells in the S phase of the cell cycle during 1 to 2 days of subjugation to stress. Cyclic tensile stretch also increased collagenous protein synthesis in nucleus pulposus cells during 1 to 4 days of stress. CONCLUSIONS: Mechanical stress on nucleus pulposus cells promotes the proliferation of cells and alters the properties of intervertebral disc cells. This study may reflect the adaptation of the intervertebral disc to increased motion and stress.