共查询到20条相似文献，搜索用时 15 毫秒
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Intervertebral disc degeneration is the main cause of low back pain. In the past 20 years, the injection of mesenchymal stromal cells (MSCs) into the nucleus pulposus of the degenerative disc has become the main approach for the treatment of low back pain. Despite the progress made in this field, there are still many barriers to overcome. First, intervertebral disc is a highly complex load-bearing composite tissue composed of annulus fibrosus, nucleus pulposus and cartilaginous endplates. Any structural damage will change its overall biomechanical function, thereby causing progressive degeneration of the entire intervertebral disc. Therefore, MSC-based treatment strategies should not only target the degenerated nucleus pulposus but also include degenerated annulus fibrosus or cartilaginous endplates. Second, to date, there has been relatively little research on the basic biology of annulus fibrosus and cartilaginous endplates, although their pathological changes such as annular tears or fissures, Modic changes, or Schmorl's nodes are more commonly associated with low back pain. Given the high complexity of the structure and composition of the annulus fibrosus and cartilaginous endplates, it remains an open question whether any regeneration techniques are available to achieve their restorative regeneration. Finally, due to the harsh microenvironment of the degenerated intervertebral disc, the delivered MSCs die quickly. Taken together, current MSC-based regenerative medicine therapies to regenerate the entire disc complex by targeting the degenerated nucleus pulposus alone are unlikely to be successful. 相似文献
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Charles Handley Tony Goldschlager David Oehme Peter Ghosh Graham Jenkin 《World journal of stem cells》2015,7(1):65-74
Low back pain is a common clinical problem, which leads to significant social, economic and public health costs. Intervertebral disc (IVD) degeneration is accepted as a common cause of low back pain. Initially, this is characterized by a loss of proteoglycans from the nucleus pulposus resulting in loss of tissue hydration and hydrostatic pressure. Conservative management, including analgesia and physiotherapy often fails and surgical treatment, such as spinal fusion, is required. Stem cells offer an exciting possible regenerative approach to IVD disease. Preclinical research has demonstrated promising biochemical, histological and radiological results in restoring degenerate IVDs. Cell tracking provides an opportunity to develop an in-depth understanding of stem cell survival, differentiation and migration, enabling optimization of stem cell treatment. Magnetic Resonance Imaging (MRI) is a non-invasive, non-ionizing imaging modality with high spatial resolution, ideally suited for stem cell tracking. Furthermore, novel MRI sequences have the potential to quantitatively assess IVD disease, providing an improved method to review response to biological treatment. Superparamagnetic iron oxide nanoparticles have been extensively researched for the purpose of cell tracking. These particles are biocompatible, non-toxic and act as excellent MRI contrast agents. This review will explore recent advances and issues in stem cell tracking and molecular imaging in relation to the IVD. 相似文献
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Yongren Wu Sarah Cisewski Barton L. Sachs Hai Yao 《Molecular & cellular biomechanics : MCB》2013,10(2):159-182
This study examines the effects of cartilage endplate (CEP) calcificationand the injection of intervertebral disc (IVD) cells on the nutrition distributionsinside the human IVD under physiological loading conditions using multiphasicfinite element modeling. The human disc was modeled as an inhomogeneous mixtureconsisting of a charged elastic solid, water, ions (Na+ and Cl−), and nutrient solute(oxygen,glucose and lactate) phases. The effect of the endplate calcification was simulated by a reduction of the tissue porosity (i.e., water volume faction) from 0.60 to 0.48. The effect of cell injection was simulated by increasing the cell density in the nucleus pulposus (NP) region by 50%, 100%, and 150%. Strain-dependent transport properties(e.g., hydraulic permeability and solute diffusivities) were considered to couple the solute transport and the mechanical loading. The simulation results showed that nutrient solute distribution inside the discis maintained at a stable state during the day and night. The physiological diurnal cyclic loading does not change the nutrient environment in the human IVD. The cartilage endplate plays a significant role in the nutrient supply to human IVD. Calcification of the cartilage endplate significantly reduces the nutrient levels in human IVD. Therefore, in cell based therapy for IVD regeneration, theincreased nutrient demand as a result of cell injection needs to be addressed. Excessive numbers of injected cells may cause further deterioration of the nutrient environment in the degenerated disc. This study is important for understanding the pathology of IVD degeneration and providing new insights into cell based therapies for low back pain. 相似文献
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Gianluca Vadalà Fabrizio Russo Luca Ambrosio Mattia Loppini Vincenzo Denaro 《World journal of stem cells》2016,8(5):185-201
Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments.Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers(e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. 相似文献
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目的检测缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)和葡萄糖转运蛋白-1(glucose transporter-1,GLUT-1)在不同月龄大鼠椎间盘纤维环组织中的表达及其相关性,探讨HIF-1α及GLUT-1在椎间盘退变过程中的作用。方法取Wistar大鼠50只,分别以1,3,6,12,18个月龄分为5组。采用免疫组化法及Western blot法检测各组椎间盘中HIF-1α和GLUT-1表达情况。结果随着大鼠月龄的增长,其椎间盘纤维环组织中HIF-1α和GLUT-1的表达也发生变化,由低月龄组(1-3月龄)至成年组(6-12月龄)HIF-1α和GLUT-1表达逐渐减少,而老年组(18月龄)二者表达显著增加。且这种变化有显著统计学意义(P0.01)。纤维环中HIF-1α和GLUT-1的蛋白表达呈正相关。结论HIF-1α、GLUT-1表达水平的变化与椎间盘退变的发生关系密切相关,HIF-1α可以通过上调GLUT-1等相关因子并延缓椎间盘退变,可能作为椎间盘退变治疗研究的切入点。 相似文献
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Zhi-Lei Hu Hai-Yin Li Xian Chang Yue-Yang Li Chen-Hao Liu Xiao-Xin Gao Yu Zhai Yu-Xuan Chen Chang-Qing Li 《World journal of stem cells》2020,12(8):803-813
Intervertebral disc (IVD) degenerative diseases are a common problem in the world, and they cause substantial social and economic burdens for people. The current methods for treating IVD degenerative diseases mainly include surgery and conservative treatment, which cannot fundamentally restore the normal structure of the disc. With continuous research on the mechanism of degeneration and the development of regenerative medicine, rapid progress has been made in the field of regenerative medicine regarding the use of stem cell-derived exosomes, which are active biological substances used in intercellular communication, because they show a strong effect in promoting tissue regeneration. The study of exosomes in the field of IVD degeneration has just begun, and many surprising achievements have been made. This paper mainly reviews the biological characteristics of exosomes and highlights the current status of exosomes in the field of IVD degeneration, as well as future developments regarding exosomes. 相似文献
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近年来,关于胶质细胞有许多令人惊奇的发现。其中最令人感兴趣的是部分胶质细胞在体内外都表现出神经千细胞／祖细胞的特性,在适当条件下能分化成神经元、星形胶质细胞和／或少突胶质细胞。不仅存在于非哺乳类脊椎动物整个生命周期的放射胶质显示出这一特性,存在于成年哺乳动物脑室下区和颗粒下层的星形胶质细胞也是如此。在体外培养中,部分胶质细胞具有形成多潜能神经球的能力。在体内,胶质细胞充当前驱细胞时的命运受到细胞间相互作用、细胞因子、血脉系统、胞外基质以及基膜等所构建的微环境的影响。胶质细胞的这些特性将对神经修复产生深远影响。 相似文献
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Demissew Shenegelegn Mern Tanja Walsen Anja Beierfuß Claudius Thom 《Experimental biology and medicine (Maywood, N.J.)》2021,246(4):483
Degenerative disc disease (DDD) is a painful, chronic and progressive disease, which is characterized by inflammation, structural and biological deterioration of the intervertebral disc (IVD) tissues. DDD is specified as cell-, age-, and genetic-dependent degenerative process that can be accelerated by environmental factors. It is one of the major causes of chronic back pain and disability affecting millions of people globally. Current treatment options, such as physical rehabilitation, pain management, and surgical intervention, can provide only temporary pain relief. Different animal models have been used to study the process of IVD degeneration and develop therapeutic options that may restore the structure and function of degenerative discs. Several research works have depicted considerable progress in understanding the biological basis of disc degeneration and the therapeutic potentials of cell transplantation, gene therapy, applications of supporting biomaterials and bioactive factors, or a combination thereof. Since animal models play increasingly significant roles in treatment approaches of DDD, we conducted an electronic database search on Medline through June 2020 to identify, compare, and discuss publications regarding biological therapeutic approaches of DDD that based on intradiscal treatment strategies. We provide an up-to-date overview of biological treatment strategies in animal models including mouse, rat, rabbit, porcine, bovine, ovine, caprine, canine, and primate models. Although no animal model could profoundly reproduce the clinical conditions in humans; animal models have played important roles in specifying our knowledge about the pathophysiology of DDD. They are crucial for developing new therapy approaches for clinical applications. 相似文献
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Chencheng Feng Huan Liu Minghui Yang Yang Zhang Bo Huang 《Cell cycle (Georgetown, Tex.)》2016,15(13):1674-1684
The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD. 相似文献
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Sobia Ekram Shumaila Khalid Asmat Salim Irfan Khan 《World journal of stem cells》2021,13(12):1881-1904
Lower back pain is a leading cause of disability and is one of the reasons for the substantial socioeconomic burden. The etiology of intervertebral disc (IVD) degeneration is complicated, and its mechanism is still not completely unde
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目的:探讨退行性腰椎滑脱(DLS)临近节段椎间盘退变程度和关节突关节角度之间的关系。方法:选取我院2012年6月至2016年6月收治的120例DLS患者作为DLS组,另外选取来我院接受体检的健康者120例作为对照组,选择CT进行关节突关节角和腰椎滑脱度的测量,使用MRI的T2像对椎间盘进行Pfirrmann退变分级。结果:DLS组的各节段关节突关节角度均小于对照组(P0.05);DLS组不同滑脱程度的L2/3、L3/4、L5/S1节段关节突关节角度的比较,差异无统计学意义(P0.05);DLS组L2/3、L3/4、L5/S1节段不同椎间盘退变等级间的滑脱程度无显著性差异(P0.05)。L2/3和L3/4节段不同椎间盘退变程度间关节突关节角度差无显著性差异(P0.05),L5/S1节段不同椎间盘退变程度间关节突关节角度差有统计学差异(P0.05)。结论:退行性腰椎滑脱临近节段关节突关节角度明显小于正常人,且临近节段关节突关节的角度并未随着腰椎滑脱程度的加重而改变,退行性腰椎滑脱患者滑脱临近节段椎间盘退变与关节突关节的矢状化程度无关,但L5/S1关节突关节角度不对称性会影响到同节段椎间盘退变程度。 相似文献
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目的:探究白细胞介素-17(interleukin-17,IL-17)对体外培养髓核细胞增殖和细胞代谢的影响。方法:髓核细胞取自经核磁共振影像确认需手术的退变椎间盘组织,建立体外培养体系。用2、5、10、15、20 ng/mL IL-17刺激髓核细胞72 h后,MTS法检测细胞增殖情况。用适当浓度IL-17刺激细胞48 h或96 h后,采用实时定量-PCR和免疫印迹方法检测基质和组织代谢相关基因的mRNA和蛋白表达。结果:IL-17刺激可以抑制体外培养髓核细胞的增殖,且15 ng/mL浓度的抑制作用最强。15 ng/mL IL-17刺激髓核细胞后,聚集蛋白聚糖(aggrecan,ACAN)和I型胶原(type I collagen,COL1A1)mRNA表达水平显著下降(P0.05),基质金属蛋白酶(matrix metalloproteinase-3,MMP3)、金属蛋白酶3组织抑制剂(tissue inhibitor of metalloproteinase-3,TIMP3)的mRNA表达水平显著上升(P0.05)。COL2A1 mRNA的表达下降,MMP13、含Ⅰ型血小板结合蛋白基序的结聚蛋白样金属蛋白酶(a disintegrin like and metalloproteinase with thrombospondin typeⅠ motifs-4,ADAMTS4)、ADAMTS5、TIMP1 mRNA的表达上升,但差异均不显著(P0.05)。IL-17刺激48 h时,COL1A1的蛋白水平明显下降(P=0.010),而ADAMTS5的蛋白水平显著上升(P=0.005)。但刺激96h时,COL1A1的蛋白表达下降,ADAMTS5的蛋白表达上升,但无显著差异(P0.05);COL2A1的蛋白表达水平显著下降(P=0.037)。结论:IL-17可抑制体外培养髓核细胞的增殖及代谢,在椎间盘的退变过程中可能发挥了重要的促进作用。 相似文献
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Sujun Qiu Changgui Shi Arivarasu Natarajan Anbazhagan Vaskar Das Vipin Arora Ranjan Kc Xin Li InSug O-Sullivan Andre van Wijnen Sudhakar Chintharlapalli Gina Gott-Velis Ripper Richard Fackson Mwale Masabumi Shibuya Shaoxiong Min Hee-Jeong Im 《Journal of cellular physiology》2020,235(6):5305-5317
Although degenerative disc disease (DDD) and related low back pain (LBP) are growing public health problems, the underlying disease mechanisms remain unclear. An increase in the vascular endothelial growth factor (VEGF) levels in DDD has been reported. This study aimed to examine the role of VEGF receptors (VEGFRs) in DDD, using a mouse model of DDD. Progressive DDD was induced by anterior stabbing of lumbar intervertebral discs in wild type (WT) and VEGFR-1 tyrosine-kinase deficient mice (vegfr-1TK−/−). Pain assessments were performed weekly for 12 weeks. Histological and immunohistochemical assessments were made for discs, dorsal root ganglions, and spinal cord. Both vegfr-1TK−/− and WT mice presented with similar pathological changes in discs with an increased expression of inflammatory cytokines and matrix-degrading enzymes. Despite the similar pathological patterns, vegfr-1TK−/− mice showed insensitivity to pain compared with WT mice. This insensitivity to discogenic pain was related to lower levels of pain factors in the discs and peripheral sensory neurons and lower spinal glial activation in the vegfr-1TK−/− mice than in the WT mice. Exogenous stimulation of bovine disc cells with VEGF increased inflammatory and cartilage degrading enzyme. Silencing vegfr-1 by small-interfering-RNA decreased VEGF-induced expression of pain markers, while silencing vegfr-2 decreased VEGF-induced expression of inflammatory and metabolic markers without changing pain markers. This suggests the involvement of VEGFR-1 signaling specifically in pain transmission. Collectively, our results indicate that the VEGF signaling is involved in DDD. Particularly, VEGFR-1 is critical for discogenic LBP transmission independent of the degree of disc pathology. 相似文献
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目的:优化人原代髓核细胞的体外分离培养方法,为椎间盘退变的防治研究提供种子细胞。方法:无菌环境中摘取人椎间盘髓核组织,采用多次胶原酶消化法分离提取原代人髓核细胞,置于5%CO2培养箱中37℃恒温培养,倒置相差显微镜中观察细胞形态,采用MTT法绘制细胞生长曲线,甲苯胺蓝染色法检测髓核细胞内蛋白多糖的表达情况,细胞免疫荧光染色法检测Ⅱ型胶原蛋白表达情况。结果:本研究中获得的细胞形态不规则,呈梭形或多角形,原代细胞48 h内贴壁,培养第8天左右细胞融合度可达90%,第三代细胞12 h内即可贴壁,生长至融合90%约需5d。甲苯胺蓝染色及细胞免疫荧光染色均阳性,提示所得细胞具有分泌蛋白多糖及Ⅱ型胶原蛋白的功能。结论:改良胶原酶消化法可获得大量纯净的人髓核细胞,提高培养效率,原代及传代细胞具备类软骨细胞表型,且活性及功能均较为稳定,可作为椎间盘组织工程研究的种子细胞。 相似文献
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目的:探讨mi R-155对人椎间盘退变髓核细胞凋亡的影响及其作用机制。方法:首先构建慢病毒表达载体,在293T细胞中获得重组慢病毒,然后感染椎间盘退变髓核细胞得到稳定过表达细胞系,同时设置空载体和空白细胞组对照。用荧光显微镜观察慢病毒载体的标签蛋白GFP的表达,分别提取三组细胞总RNA,采用RT-q PCR方法检测mi R-155的表达;通过流式细胞术检测细胞凋亡,Western-Blot检测细胞中凋亡相关蛋白FADD、Caspase-3、Bcl-2及Bax的表达,JC-1试剂盒检测细胞线粒体膜电位的变化情况。结果:在荧光显微镜下,经慢病毒感染的过表达细胞系和空载体细胞系均出现绿色荧光,而空白细胞组未见绿色荧光;RT-qPCR结果显示构建的稳定过表达细胞系(GV369-miR-155-NP)中mi R-155的表达水平较高,且与空载体细胞系及空白细胞对照组均呈显著性差异(P0.05);与空载体组(GV369-NP)及空白细胞对照组相比,过表达组(GV369-miR-155-NP)细胞凋亡率显著降低(P0.05),FADD、Caspase-3、Bax的表达水平均明显下降,而Bcl-2表达水平显著增加(P0.05)。结论:mi R-155可能通过靶向结合Caspase-3和FADD阻止FasL-Fas途径或通过线粒体途径抑制人椎间盘退变髓核细胞凋亡。 相似文献
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Zheng Li Xingye Li Chong Chen Shugang Li Jianxiong Shen Gary Tse Matthew T. V. Chan William K. K. Wu 《Cell proliferation》2018,51(5)
Intervertebral disc degeneration (IDD) is the major cause of low back pain which incurs a significant public‐health and economic burden. The aetiology of IDD is complex, with developmental, genetic, biomechanical and biochemical factors contributing to the disease development. Deregulated phenotypes of nucleus pulposus cells, including aberrant differentiation, apoptosis, proliferation and extracellular matrix deposition, are involved in the initiation and progression of IDD. Non‐coding RNAs, including long non‐coding RNAs (lncRNAs), have recently been identified as important regulators of gene expression. Research into their roles in IDD has been very active over the past 5 years. Our review summarizes current research regarding the roles of deregulated lncRNAs (eg, RP11‐296A18.3, TUG1, HCG18) in modulating nucleus pulposus cell functions in IDD. These exciting findings suggest that specific modulation of lncRNAs or their downstream signalling pathways might be an attractive approach for developing novel therapeutics for IDD. 相似文献
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There is now strong evidence that the stem cells of many tissues reside in specialized structures termed niches. The stem cell niche functions to house and regulate symmetric and asymmetric mitosis of stem cells in mammalian skin, mouse and human bone marrow, mouse brain, gut, and hair follicle, and Drosophila ovary and testis. This regulation is effected through the action of various signaling pathways such as Notch, Hedgehog, Wnt and others. The hormones of the estrous cycle, pregnancy and lactation that initiate growth in mouse mammary epithelium appear to act at a paracrine level to regulate mitosis through Notch receptors. Previous work has established that the putative stem cells of the mammary epithelium in several animal species reside near the basement membrane and never make contact with the ductal lumen. We show that these putative stem cells are found in anatomically specialized places created by the cytoplasmic extensions and modifications of neighboring differentiated cells. Such specializations may help to regulate stem cell activity by modulating molecular traffic to putative stem cells and contact with signaling molecules in the basement membrane. The histological characteristics of these putative niches vary as to the kinds of relationships the cells can have with the basement membrane and neighboring cells and as to how many stem or progenitor cells they may contain. This suggests a plasticity that may be relevant to the response of niches to tissue demands, such as wound healing, the periodic growth and regression of mammary epithelium, the process of mammary tumorigenesis therapeutic strategies for breast cancer. 相似文献