磁共振扩散张量成像序列对脊髓型颈椎病的诊断价值

目的:分析3.0T磁共振（MR）扩散张量成像（DTI）序列对脊髓型颈椎病（CSM）的诊断价值。方法:选择福建中医药大学附属康复医院收治的30例CSM患者纳入观察组,另选择同期体检人群中年龄匹配的30例健康志愿者为对照组,均运用常规MRI序列及DTI技术进行扫描,运用DTI技术测量FA及ADC值,进行图像后处理及数据分析,观察组患者根据MR平扫结果分为A组（n=10,单纯硬膜囊受压）、B组（n=14,颈髓受压,信号正常）和C组（n=6,颈髓受压,T2WI高信号）,分析各组FA及DA值差异,评价DTI诊断脊髓型颈椎病的诊断价值。结果:对照组脊髓C2-3、C3-4、C4-5、C5-6、C6-7节段的ADC值与FA比较差异无统计学意义（P>0.05）;对照组与A、B、C组的ADC值、FA值存在显著性差异（P<0.05）,B组、C组的ADC值显著高于对照组（P<0.05）,FA值显著低于对照组（P<0.05）,A组ADC值、FA值与对照组比较差异无统计学意义（P>0.05）;从A组到C组,ADC值呈升高趋势,FA值呈降低趋势,差异显著（P<0.05）;MR T2WI、DTI序列扫描FA值、MR DTI序列扫描ADC值诊断扫描诊断CSM的敏感度与特异度为20.00%（6/30）与80.00%（24/30）,80.00%（24/30）与20.00%（6/30）,66.67%（20/30）与30.00%（9/30）。结论:DTI较常规MRI能更早期而准确地诊断CSM,是一种显示CSM病变和观察病变修复过程的有效手段。     

腰椎间盘的扩散张量成像观测及临床应用

目的　为腰椎间盘退变导致的腰腿痛等病症的临床诊断提供影像学依据。 方法　选取脊柱腰段扩散张量成像（DTI）扫描检查正常者200例和腰椎间盘退变者100例,在工作站划分腰椎间盘和腰椎间盘退变的感兴趣区,测量感兴趣区的表观扩散系数（ADC）和各向异性分数（FA）,比较不同解剖部位、年龄组腰椎间盘和不同Pfirrmann分级腰椎间盘退变的FA、ADC值。 结果　不同解剖部位腰椎间盘的FA值和ADC值均有统计学差异（P<0.05）,L1~2、L2~3、L3~4椎间盘的FA值逐渐降低,L4~5、L5~S1椎间盘的FA值则逐渐增高;L1~2、L2~3、L3~4椎间盘的ADC值逐渐增高,L3~4、L4~5、L5~S1椎间盘的ADC值则无明显变化。不同年龄组腰椎间盘的FA值无统计学差异（P>0.05）,ADC值有统计学差异（P<0.05）,随着年龄增长ADC值逐渐降低。不同Pfirrmann分级腰椎间盘退变的FA值和ADC值均有统计学差异（P<0.05）,随着Pfirrmann分级增高,FA值逐渐增高,ADC值逐渐降低。 结论　解剖部位、年龄均影响腰椎间盘的ADC值,DTI的FA值和ADC值可以定量评估腰椎间盘及其退变程度,为早期腰椎间盘退变的临床诊断提供影像学依据。     

腰椎间盘的扩散张量成像观测及临床应用

目的　为腰椎间盘退变导致的腰腿痛等病症的临床诊断提供影像学依据。 方法　选取脊柱腰段扩散张量成像（DTI）扫描检查正常者200例和腰椎间盘退变者100例,在工作站划分腰椎间盘和腰椎间盘退变的感兴趣区,测量感兴趣区的表观扩散系数（ADC）和各向异性分数（FA）,比较不同解剖部位、年龄组腰椎间盘和不同Pfirrmann分级腰椎间盘退变的FA、ADC值。 结果　不同解剖部位腰椎间盘的FA值和ADC值均有统计学差异（P<0.05）,L1~2、L2~3、L3~4椎间盘的FA值逐渐降低,L4~5、L5~S1椎间盘的FA值则逐渐增高;L1~2、L2~3、L3~4椎间盘的ADC值逐渐增高,L3~4、L4~5、L5~S1椎间盘的ADC值则无明显变化。不同年龄组腰椎间盘的FA值无统计学差异（P>0.05）,ADC值有统计学差异（P<0.05）,随着年龄增长ADC值逐渐降低。不同Pfirrmann分级腰椎间盘退变的FA值和ADC值均有统计学差异（P<0.05）,随着Pfirrmann分级增高,FA值逐渐增高,ADC值逐渐降低。 结论　解剖部位、年龄均影响腰椎间盘的ADC值,DTI的FA值和ADC值可以定量评估腰椎间盘及其退变程度,为早期腰椎间盘退变的临床诊断提供影像学依据。     

基于Windows平台的扩散张量成像后处理软件性能的比较

应用网络自由获取的基于Windows平台的DTI Task Card、dTV、DTIstudio、MedINRIA等4种自由扩散张量后处理软件,对同组DTI数据后处理及各向异性(FA)和表观扩散系数(ADC)测量值比较,寻找合适的不依赖于MR系统平台的后处理方法。采集18例健康志愿者和12例额顶部脑膜瘤患者术前全颅扩散张量成像数据,4种后处理软件以患者数据参照调整DTI梯度表后生成扩散张量特征图像,DTI Task Card依赖MR系统平台,余3种在PC机上应用后处理软件依赖于CPU运算。DTIstudio法在多核系统中处理时间最短,CPU占用率最低。利用4种方法重复测定胼胝体膝部、压部,双侧内囊膝部、后肢,双侧丘脑、壳核相同大小兴趣区的FA值和ADC值,总体均数间不具显著性差异,以DTIstudio法测定值与DTI Task Card法测定值间相关性最高。DTIstudio是一种理想的、不依赖于MR系统软件的DTI后处理量值测定软件。     

3.0 T磁共振T2WI IDEAL及DTI在腰椎间盘退行性变中应用

目的 探讨3.0 T磁共振T₂加权成像(T₂WI)、三点法非对称回波水脂分离(IDEAL)成像及扩散张量成像(DTI)在腰椎间盘退行性变评估中的应用价值。方法 选择100例腰椎间盘退行性变患者，其中男性51例，女性49例；年龄14～85岁，平均年龄49.4岁；病程1天～3年，平均病程(65.0±16.2)天；发生椎间盘突出部位L_1/2椎间盘2例，L_2/3椎间盘7例，L_3/4椎间盘23例，L_4/5椎间盘56例，L₅/S₁椎间盘48例。采用T₂WI IDEAL水相位图根据Pfirrmann分级标准对椎间盘进行分级，并测量各椎间盘T₂信号强度(T₂SI)。采用矢状位DTI图测量各椎间盘部分各向异性系数(FA)及表观扩散系数(ADC)。比较椎间盘不同Pfirrmann分级间FA、ADC值及T₂SI，并统计分析FA、ADC值及T     

3.OT MR三维重建脑干小脑上脚纤维交叉的研究

目的 应用3.0T MR扩散张量成像(DTI)和白质纤维成像技术(DTT),研究脑干小脑上脚纤维(SCP)交叉的微观结构和特性.方法 Siemens 3.0T MR对20例健康志愿者行头颅轴位DTI (b=0和b=1000)检查,应用工作站纤维束跟踪软件三维重建脑干SCP纤维交叉,选择参数:FA为0.08、角度阈值为80°、体素为1.2 mm×1.2 mm×3 mm.测量SCP和SCP交叉的各向异性分数(FA)值,比较两者之间的差异.结果 脑干SCP纤维交叉出现三种不同形态:(1)交叉,占65％(13例);(2)对吻,占25％(5例);(3)分叉,占10％(2例).SCP交叉和SCP的FA值分别为:0.40±0.13和0.65±0.08,两者之间差异有统计学意义( t=7.22,P＜0.05)结论 DTT三维重建技术能显示脑干SCP交叉纤维束的解剖类型,3.0T MR对于活体脑干交叉纤维束的研究有较好的临床应用价值.     

磁共振弥散张量成像联合纤维束成像在脑梗死中的应用研究

目的 分析脑梗死患者磁共振弥散张量成像(DTI)和纤维束成像(DTT)的特点,探讨DTI、DTT在对不同时期脑梗死患者诊断的价值。方法分别对58例不同时期脑梗死患者和25名健康志愿者行MRI检查,包括T1WI、T2WI成像、FLAIR及DTI成像,重建部分各向异性(FA)图,对梗死区、健侧相应部位及正常对照组相应部位进...     

磁共振弥散张量成像对瘤样炎性脱髓鞘病与低级别胶质瘤鉴别诊断的研究

目的 探讨MR弥散张量成像(DTI)在瘤样炎性脱髓鞘病(TIDD)与低级别胶质瘤(LGG)鉴别诊断中的应用价值。方法 纳入2012年1月—2016年2月在重庆医科大学附属第一医院确诊的10例TIDD患者及15例经病理证实的LGG患者资料进行回顾性分析。所有患者行3.0 T MR DTI检查,在表观弥散系数(ADC) 图及部分各向异性(FA) 图上定量测定患者病变区及其对侧镜像部位正常脑白质区(镜像区)的 ADC 值及 FA值,并进行统计分析;同时重建白质纤维素的3D图像,观察白质纤维素与病变区的空间位置关系。结果 TIDD组病变区和镜像区的ADC值、FA值分别为(1.484±0.14)×10³ mm²/s、0.109±0.02和(0.725±0.05)×10³ mm²/s、0.443±0.08,LGG组病变区和镜像区的ADC值、FA值分别为(1.368±0.09)×10³ mm²/s、0.163±0.01和(0.684±0.03)×10³ mm²/s、0.471±0.04。TIDD组与LGG组两组内病变区与镜像区ADC值和FA值差异均有统计学意义 (P值均<0.01),组间病变区ADC值和FA值差异均有统计学意义(P值均<0.05)。LGG的纤维重建图主要表现为肿瘤部位明显受压外移,较对侧稀疏、中断及形态改变;TIDD的纤维重建图主要表现为纤维稍稀疏,未见明显中断及移位改变。结论 TIDD与LGG在DTI上的弥散指标存在明显差异,可为两者的鉴别诊断提供量化依据。     

MR扩散张量成像和纤维束示踪技术评价经阴道分娩初产妇肛提肌损伤

目的 探讨MR扩散张量成像(DTI)和纤维束示踪技术在经阴道分娩初产妇肛提肌损伤评价中的应用价值,为产后盆底康复治疗及盆腔器官脱垂的预防提供客观依据。方法 纳入2014年6月—2015年1月在天津市第一中心医院经阴道自然分娩后6个月初产妇50名(观察组),无症状未孕未产志愿者33名(对照组)进行前瞻性研究。受试者行盆底横断面、冠状面FSE T₂WI MR及DTI检查。对DTI图像进行后处理获得肛提肌各分支(耻骨内脏肌、髂尾肌)的3D肌肉纤维束图像,并评价其纤维示踪的精确性,对能够得到较为精确纤维束示踪图像者测量其各向异性分数(FA)、表观扩散系数(ADC)值。应用FSE T₂WI MRI影像评价产妇肛提肌损伤情况,并将其分为耻骨内脏肌无损伤组、耻骨内脏肌损伤组,采用方差分析比较对照组、无损伤组及损伤组间FA、ADC值的差异。结果 2组受试者均获得较为精确的耻骨内脏肌3D肌肉纤维束图像及对应的FA及ADC值,而髂尾肌3D肌肉纤维束图像均不精确。12例(24.0%,12/50)产妇存在耻骨内脏肌损伤,其中9例表现为单侧部分缺损,3例表现为双侧萎缩;4例(8.0%,4/50)产妇存在髂尾肌损伤,均表现为单侧部分缺损。对照组未发现肛提肌损伤。对照组、耻骨内脏肌无损伤组和损伤组耻骨内脏肌的FA值分别为0.49±0.08、0.52±0.11、0.53±0.13,ADC值分别为(1.79±0.29)×10^-3 mm²/s、(1.75±0.34)×10^-3 mm²/s、(1.93±0.35)×10^-3 mm²/s,差异均无统计学意义(F=1.217、1.747, P值均>0.05)。结论 DTI纤维束成像能够3D显示耻骨内脏肌纤维束结构,但髂尾肌的显示较为困难。目前DTI尚不能准确定量诊断肛提肌损伤情况。     

应用DTI技术对人脑白质纤维束的初步研究

目的建立扩散张量纤维束成像对人脑白质纤维的显示方法,并应用中国数字化可视人体数据进行对照观察,验证扩散张量成像(DTI)方法的可靠性。方法选择5名健康志愿者进行DTI成像,采用DtiStudio软件进行分析处理,重建出部分各向异性(FA)图、容积比(VR)图、相对各向异性(RA)图、表面扩散系数(ADC)图以及二维彩色张量图。应用中国数字化可视人体数据集断面图像、FA图及彩色FA图进行对照观察,利用fibertracking纤维跟踪软件及3DMRI软件进行三维重建显示脑内主要白质纤维束,辨认脑内白质纤维束的位置、形态。结果应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,包括联络纤维如弓形纤维、钩束、扣带束、上纵束和下纵束,连合纤维如胼胝体、前连合和穹隆,投射纤维如锥体束、视放射、内侧丘系等。DTI纤维束成像结果与已知解剖知识、中国可视化人体断面图像具有很好的一致性。结论应用DTI纤维束成像可以清晰准确地描绘脑白质内主要神经纤维束的解剖图谱,其结果与中国可视化人体断面图像、已知解剖知识是一致的,应用DTI纤维束成像研究脑内纤维连通性是可靠的。     

Anisotropic Diffusive Transport in Annulus Fibrosus: Experimental Determination of the Diffusion Tensor by FRAP Technique

The annulus fibrosus (AF) of the intervertebral disc (IVD) exhibits a fiber-organized structure which is responsible for anisotropic and inhomogeneous mechanical and transport properties. Due to its particular morphology, nutrient transport within AF is regulated by complex transport kinetics. This work investigates the diffusive transport of a small solute in the posterior and anterior regions of AF since diffusion is the major transport mechanism for low molecular weight nutrients (e.g., oxygen and glucose) in IVD. Diffusion coefficient (D) of fluorescein (332 Da) in bovine coccygeal AF was measured in the three major (axial, circumferential, and radial) directions of the IVD by means of fluorescence recovery after photobleaching (FRAP) technique. It was found that the diffusion coefficient was anisotropic and inhomogeneous. In both anterior and posterior regions, the diffusion coefficient in the radial direction was found to be the lowest. Circumferential and axial diffusion coefficients were not significantly different in both posterior and anterior regions and their values were about 130% and 150% the value of the radial diffusion coefficient, respectively. The values of diffusion coefficients in the anterior region were in general higher than those of corresponding diffusion coefficients in the posterior region. This study represents the first quantitative analysis of anisotropic diffusion transport in AF by means of FRAP technique and provides additional knowledge on understanding the pathways of nutritional supply into IVD.     

Intervertebral disk tissue engineering using biphasic silk composite scaffolds

Scaffolds composed of synthetic, natural, and hybrid materials have been investigated as options to restore intervertebral disk (IVD) tissue function. These systems fall short of the lamellar features of the native annulus fibrosus (AF) tissue or focus only on the nucleus pulposus (NP) tissue. However, successful regeneration of the entire IVD requires a combination approach to restore functions of both the AF and NP. To address this need, a biphasic biomaterial structure was generated by using silk protein for the AF and fibrin/hyaluronic acid (HA) gels for the NP. Two cell types, porcine AF cells and chondrocytes, were utilized. For the AF tissue, two types of scaffold morphologies, lamellar and porous, were studied with the porous system serving as a control. Toroidal scaffolds formed out of the lamellar, and porous silk materials were used to generate structures with an outer diameter of 8 mm, inner diameter of 3.5 mm, and a height of 3 mm (the interlamellar distance in the lamellar scaffold was 150-250 μm, and the average pore sizes in the porous scaffolds were 100-250 μm). The scaffolds were seeded with porcine AF cells to form AF tissue, whereas porcine chondrocytes were encapsulated in fibrin/HA hydrogels for the NP tissue and embedded in the center of the toroidal disk. Histology, biochemical assays, and gene expression indicated that the lamellar scaffolds supported AF-like tissue over 2 weeks. Porcine chondrocytes formed the NP phenotype within the hydrogel after 4 weeks of culture with the AF tissue that had been previously cultured for 2 weeks, for a total of 6 weeks of cultivation. This biphasic scaffold simulating in combination of both AF and NP tissues was effective in the formation of the total IVD in vitro.     

Nutrient Transport in Human Annulus Fibrosus is Affected by Compressive Strain and Anisotropy

The avascular intervertebral disc (IVD) receives nutrition via transport from surrounding vasculature; poor nutrition is believed to be a main cause of disc degeneration. In this study, we investigated the effects of mechanical deformation and anisotropy on the transport of two important nutrients??oxygen and glucose??in human annulus fibrosus (AF). The diffusivities of oxygen and glucose were measured under three levels of uniaxial confined compression??0, 10, and 20%??and in three directions??axial, circumferential, and radial. The glucose partition coefficient was also measured at three compression levels. Results for glucose and oxygen diffusivity in AF ranged from 4.46?×?10^?7 to 9.77?×?10^?6?cm²/s and were comparable to previous studies; the glucose partition coefficient ranged from 0.71 to 0.82 and was also similar to previous results. Transport properties were found to decrease with increasing deformation, likely caused by fluid exudation during tissue compression and reduction in pore size. Furthermore, diffusivity in the radial direction was lower than in the axial or circumferential directions, indicating that nutrient transport in human AF is anisotropic. This behavior is likely a consequence of the layered structure and unique collagen architecture of AF tissue. These findings are important for better understanding nutritional supply in IVD and related disc degeneration.     

Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.     

Monitoring of the effect of intervertebral disc nucleus pulposus ablation by MRI

In order to investigate intervertebral disc (IVD) degeneration and repair, a quantitative non‐invasive tool is needed. Various MRI methods including qCPMG, which yields dipolar echo relaxation time (T_DE), magnetization transfer contrast (MTC), and ¹H and ²H double quantum filtered (DQF) MRI were used in the present work to monitor changes in rat IVD after ablation of the nucleus pulposus (NP), serving as a model of severe IVD degeneration. In the intact IVD, a clear distinction between the annulus fibrosus (AF) and the NP is obtained on T₂ and T_DE weighted images as well as on MTC maps, reflecting the high concentration of ordered collagen fibers in the AF. After ablation of the NP, the distinction between the compartments is lost. T₂ and T_DE relaxation times are short throughout the disc and MTC is high. ¹H and ²H DQF signal, which in intact discs is obtained only for the AF, is now observable throughout the tissue. These results indicate that after ablation, there is an ingression of collagen fibers from the AF into the area that was previously occupied by the NP, as was confirmed by histology. Copyright © 2010 John Wiley & Sons, Ltd.     

Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells–fibrin suspension and polymerized by dropping thrombin–sodium chloride (CaCl₂) solution. A PLGA–cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold–cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.     

Potential biomarkers of the mature intervertebral disc identified at the single cell level

Intervertebral disc (IVD) degeneration and trauma is a major socio‐economic burden and the focus of cell‐based regenerative medicine approaches. Despite numerous ongoing clinical trials attempting to replace ailing IVD cells with mesenchymal stem cells, a solid understanding of the identity and nature of cells in a healthy mature IVD is still in need of refinement. Although anatomically simple, the IVD is comprised of heterogeneous cell populations. Therefore, methods involving cell pooling for RNA profiling could be misleading. Here, by using RNA in situ hybridization and z proportion test, we have identified potential novel biomarkers through single cell assessment. We quantified the proportion of RNA transcribing cells for 50 genetic loci in the outer annulus fibrosus (AF) and nucleus pulposus (NP) in coccygeal bovine discs isolated from tails of four skeletally mature animals. Our data reconfirm existing data and suggest 10 novel markers such as Lam1 and Thy1 in the outer AF and Gli1, Gli3, Noto, Scx, Ptprc, Sox2, Zscan10 and LOC101904175 in the NP, including pluripotency markers, that indicate stemness potential of IVD cells. These markers could be added to existing biomarker panels for cell type characterization. Furthermore, our data once more demonstrate heterogeneity in cells of the AF and NP, indicating the need for single cell assessment by methods such as RNA in situ hybridization. Our work refines the molecular identity of outer AF and NP cells, which can benefit future regenerative medicine and tissue engineering strategies in humans.     

Role of growth differentiation factor-5 and bone morphogenetic protein type II receptor in the development of lumbar intervertebral disc degeneration

The present study was designed to evaluate the role of growth differentiation factor-5 (GDF-5) and bone morphogenetic protein type II receptor (BMPR-II) in the development of lumbar intervertebral disc degeneration (IDD). A total of 24 patients with lumbar IDD (experiment group) and 6 patients with lumbar vertebral fracture (control group) were enrolled in the study. Tissue samples of IVD from the experiment group and control group were obtained during lumbar fusion operation, respectively. Fixation and decalcification of IVD tissue were performed, and then HE staining was carried out to observe the morphological changes of the lumbar IVD tissues. The expression of GDF-5 and BMPRII in human lumbar IVD was detected by immunohistochemical staining. HE staining results showed that non- and minimal degeneration was found in 11 cases (score range, 0-3), moderate degeneration in 12 cases (score range, 4-8), and severe degeneration in 7 cases (score range, 9-12). According to the immunohistochemical results, the positive expression rates of GDF-5 and BMPRII in NP were higher than those in AF of the non- and minimal degeneration group, moderate degeneration group and severe degeneration group (all P < 0.05). However, no significant difference in GDF-5 or BMPRII positive expression was observed among the normal, non- and minimal, moderate and severe degeneration groups in neither NP area nor AF area (all P > 0.05). In conclusion, our results showed that GDF-5 and BMPRII expressed both in normal and degenerated IVD tissues, and GDF-5 might have an inhibition effect on degenerated lumbar IVD, suggesting that gene therapy may be a useful approach in producing physiological effects during early- and late-phase of lumbar IDD.     

Diversity of intervertebral disc cells: phenotype and function

The intervertebral disc (IVD) is a moderately moving joint that is located between the bony vertebrae and provides flexibility and load transmission throughout the spinal column. The disc is composed of different but interrelated tissues, including the central highly hydrated nucleus pulposus (NP), the surrounding elastic and fibrous annulus fibrosus (AF), and the cartilaginous endplate (CEP), which provides the connection to the vertebral bodies. Each of these tissues has a different function and consists of a specific matrix structure that is maintained by a cell population with distinct phenotype. Although the healthy IVD is able to balance the slow matrix turnover of synthesis and degradation, this balance is often disturbed, leading to degenerative disorders. Successful therapeutic management of IVD degeneration requires a profound understanding of the cellular and molecular characteristics of the functional IVD. Hence, the phenotype of IVD cells has been of significant interest from multiple perspectives, including development, growth, remodelling, degeneration and repair. One major challenge that complicates our understanding of the disc cells is that both the cellular phenotype and the extracellular matrix strongly depend on disc maturity and health and as a consequence are continuously evolving. This review delineates the diversity of the cell types found in the intervertebral disc, with emphasis on human, but with reference to other species. The cells of the NP appear rounded and express a proteoglycan-rich matrix, whereas the more elongated AF cells are embedded in a collagen fibre matrix and the CEPs represent a layer of cartilage. Even though all disc cells have often been referred to as ‘intervertebral disc chondrocytes’, distinct phenotypical differences in comparison with articular chondrocytes exist and have been reported recently. The availability of more specific markers has also improved our understanding of progenitor cell differentiation towards an IVD cell phenotype. Ultimately, new cell- and tissue-engineering approaches to regenerative therapies will only be successful if the specific characteristics of the individual tissues and their context in the function of the whole organ, are taken into consideration.