Osmosis and viscoelasticity both contribute to time-dependent behaviour of the intervertebral disc under compressive load: A caprine in vitro study

The mechanical behaviour of the intervertebral disc highly depends on the content and transport of interstitial fluid. It is unknown, however, to what extent the time-dependent behaviour can be attributed to osmosis. Here we investigate the effect of both mechanical and osmotic loading on water content, nucleus pressure and disc height. Eight goat intervertebral discs, immersed in physiological saline, were subjected to a compressive force with a pressure needle inserted in the nucleus. The loading protocol was: 10 N (6 h); 150 N (42 h); 10 N (24 h). Half-way the 150 N-phase (24 h), we eliminated the osmotic gradient by adding 26% poly-ethylene glycol to the surrounding fluid. For 62 additional discs, we determined the water content of both nucleus and annulus after 6, 24, 48, or 72 h. The compressive load was initially counterbalanced by the hydrostatic pressure in the nucleus. The load forced 4.3% of the water out of the nucleus, which reduced nucleus pressure by 44(±6)%. Reduction of the osmotic gradient disturbed the equilibrium disc height, and a significant loss of annulus water content was found. Remarkably, pressure and water content of the nucleus pulposus remained unchanged. This shows that annulus water content is important in the response to axial loading. After unloading, in the absence of an osmotic gradient, there was substantial viscoelastic recovery of 53(±11)% of the disc height, without a change in water content. However, for restoration of the nucleus pressure and for full restoration of disc height, restoration of the osmotic gradient was needed.     

The effect of sustained compression on oxygen metabolic transport in the intervertebral disc decreases with degenerative changes

Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such relation, relevant to the maintenance of the tissue functional composition, would therefore link disc function with disc nutrition.     

Effect of an interspinous implant on loads in the lumbar spine.

Interspinous process implants are increasingly used to treat canal stenoses. Little information exists about the effects of implant height and stiffness on the biomechanical behavior of the lumbar spine. Therefore, a three-dimensional nonlinear finite element model of the osseoligamentous lumbar spine (L1 to L5) was created with a slightly degenerated disc at L3/L4. An interspinous implant was inserted at that segment. Implants with different heights and stiffnesses were studied. The model was loaded with the upper body weight and muscle forces to simulate walking and 25 degrees extension. Implant forces are influenced strongly by the height and negligibly by the elastic modulus of the implant. Intersegmental rotation at implant level is markedly reduced, while intradiscal pressure is slightly increased. Implant size and stiffness have only a minor effect on intradiscal pressure. The maximum von Mises stress in the vertebral arch is strongly increased by the implant.     

Diurnal variations in intervertebral disc height affect spine flexibility,intradiscal pressure and contact compressive forces in the facet joints

Diurnal changes of intervertebral disc height are caused by high compressive loading during the day, which expulses fluid from the disc, and by osmotic pressure, which imbibes fluid into the disc at low loading. The aim of the present study was to determine the magnitude of diurnal changes in spine flexibility, intradiscal pressures and contact forces in the facet joints. A validated osseoligamentous finite element model of the lumbar spine was used to determine these quantities for morning and evening situations. Disc height varied by 10% for these two situations. Spine flexibility and facet joint forces were markedly higher in the evening than in the morning. Intradiscal pressures were higher in the morning than in the evening. The different spine flexibilities in the morning and evening should be taken into account during kinematical measurements. Predicted facet joint forces may be used for the designing and pre-clinical testing of artificial facet joint replacements.     

Temporal changes of mechanical signals and extracellular composition in human intervertebral disc during degenerative progression

In this study, a three-dimensional finite element model was used to investigate the changes in tissue composition and mechanical signals within human lumbar intervertebral disc during the degenerative progression. This model was developed based on the cell-activity coupled mechano-electrochemical mixture theory. The disc degeneration was simulated by lowering nutrition levels at disc boundaries, and the temporal and spatial distributions of the fixed charge density, water content, fluid pressure, Von Mises stress, and disc deformation were analyzed. Results showed that fixed charge density, fluid pressure, and water content decreased significantly in the nucleus pulposus (NP) and the inner to middle annulus fibrosus (AF) regions of the degenerative disc. It was found that, with degenerative progression, the Von Mises stress (relative to that at healthy state) increased within the disc, with a larger increase in the outer AF region. Both the disc volume and height decreased with the degenerative progression. The predicted results of fluid pressure change in the NP were consistent with experimental findings in the literature. The knowledge of the variations of temporal and spatial distributions of composition and mechanical signals within the human IVDs provide a better understanding of the progression of disc degeneration.     

The effect of degenerative morphological changes of the intervertebral disc on the lumbar spine biomechanics: a poroelastic finite element investigation

Intervertebral disc degeneration involves changes in the spinal anatomical structures. The mechanical relevance of the following changes was investigated: disc height, endplate sclerosis, disc water content, permeability and depressurisation. A poroelastic nonlinear finite element model of the L4-L5 human spine segments was employed. Loads represented a daily cycle (500 N compression combined with flexion-extension motion for 16 h followed by 200 N compression for 8 h). In non-degenerative conditions, the model predicted a diurnal axial displacement of 1.32 mm and a peak intradiscal pressure of 0.47 MPa. Axial displacement, facet force and range of motion in flexion-extension are decreased by decreasing disc height. By decreasing the initial water content, axial displacement, facet force and fluid loss were all reduced. Endplate sclerosis did not have a significant influence on the calculated results. Depressurisation determined an increase of the disc effective stress, possibly inducing failure. Degenerative instability was not calculated in any simulations.     

The effect of degenerative morphological changes of the intervertebral disc on the lumbar spine biomechanics: a poroelastic finite element investigation

Intervertebral disc degeneration involves changes in the spinal anatomical structures. The mechanical relevance of the following changes was investigated: disc height, endplate sclerosis, disc water content, permeability and depressurisation. A poroelastic nonlinear finite element model of the L4–L5 human spine segments was employed. Loads represented a daily cycle (500 N compression combined with flexion–extension motion for 16 h followed by 200 N compression for 8 h). In non-degenerative conditions, the model predicted a diurnal axial displacement of 1.32 mm and a peak intradiscal pressure of 0.47 MPa. Axial displacement, facet force and range of motion in flexion–extension are decreased by decreasing disc height. By decreasing the initial water content, axial displacement, facet force and fluid loss were all reduced. Endplate sclerosis did not have a significant influence on the calculated results. Depressurisation determined an increase of the disc effective stress, possibly inducing failure. Degenerative instability was not calculated in any simulations.     

Analysis of the influence of disc degeneration on the mechanical behaviour of a lumbar motion segment using the finite element method

Compared to a healthy intervertebral disc, the geometry and the material properties of the involved tissues are altered in a degenerated disc. It is not completely understood how this affects the mechanical behaviour of a motion segment. In order to study the influence of disc degeneration on motion segment mechanics a three-dimensional, nonlinear finite element model of the L3/L4 functional unit was used. Different grades of disc degeneration were simulated by varying disc height and bulk modulus of the nucleus pulposus. The model was loaded with pure moments of 10Nm in the three main anatomic planes. The finite element model predicted the same trends for intersegmental rotation and intradiscal pressure as described in the literature for in vitro studies. A comparison between calculated intersegmental rotation and experimental data showed a mean difference of 1.9 degrees while the mean standard deviation was 2.5 degrees . A mildly degenerated disc increases intersegmental rotation for all loading cases. With further increasing disc degeneration intersegmental rotation is decreased. For axial rotation the decrease takes place in the final stage. Intradiscal pressure is lower while facet joint force and maximum von Mises stress in the annulus are higher in a degenerated compared to a healthy disc.     

Effect of intervertebral disc degeneration on disc cell viability: a numerical investigation

Degeneration of the intervertebral disc may be initiated and supported by impairment of the nutrition processes of the disc cells. The effects of degenerative changes on cell nutrition are, however, only partially understood. In this work, a finite volume model was used to investigate the effect of endplate calcification, water loss, reduction of disc height and cyclic mechanical loading on the sustainability of the disc cell population. Oxygen, lactate and glucose diffusion, production and consumption were modelled with non-linear coupled partial differential equations. Oxygen and glucose consumption and lactate production were expressed as a function of local oxygen concentration, pH and cell density. The cell viability criteria were based on local glucose concentration and pH. Considering a disc with normal water content, cell death was initiated in the centre of the nucleus for oxygen, glucose, and lactate diffusivities in the cartilaginous endplate below 20% of the physiological values. The initial cell population could not be sustained even in the non-calcified endplates when a reduction of diffusion inside the disc due to water loss was modelled. Alterations in the disc shape such as height loss, which shortens the transport route between the nutrient sources and the cells, and cyclic mechanical loads, could enhance cell nutrition processes.     

Expression of cartilage-derived morphogenetic protein in human intervertebral discs and its effect on matrix synthesis in degenerate human nucleus pulposus cells

Introduction  

Loss of intervertebral disc (IVD) matrix and ultimately disc height as a result of 'degeneration' has been implicated as a major cause of low back pain (LBP). The use of anabolic growth factors as therapies to regenerate IVD matrix, hence restoring disc height and thus reversing degenerative disc disease, has been suggested. Cartilage-derived morphogenetic protein (CDMP) is a growth factor which stimulates proteoglycan production in chondrocyte-like cells and thus could be a useful growth factor for LBP therapies. However, little is known about the expression of CDMP or its receptor in human IVD, nor its effects on human disc cells.     

持久脊柱负荷与椎间盘组织中MMP-2表达关系的研究

目的：建立一压力可控型椎间盘退变模型,并探讨持久的脊柱负荷对椎间盘MMP-2表达的影响。方法：选用54只成年Wistar大鼠随机分为三组,分别模拟人类在站立（A组1.12N）、坐位直立（B组1.68N）、坐位前屈（C组3.08N）三种状态下椎间盘内的负荷情况,给予大鼠尾椎Co9/10椎间盘恒定压力加压,以相邻Co8/9椎间盘不加压作为对照（D组）。三组分别在3、7、14天后取受压及对照椎间盘标本,进行HE染色组织学观察及免疫组织化学分析,观察椎间盘退变情况及MMP-2在椎间盘组织中的含量变化。结果：随时间与压力的增加,椎间盘组织学评分与MMP-2表达增高（P〈0.05）,MMP-2表达与椎间盘退变程度成正相关（r=0.870,P〈0.05）。结论：持久的脊柱负荷可引起椎间盘退变及MMP-2表达增加,MMP-2可能在椎间盘退变的过程中发挥重要作用。     

Computational study of the role of fluid content and flow on the lumbar disc response in cyclic compression: Replication of in vitro and in vivo conditions

The intervertebral disc viscoelastic response is governed primarily by its fluid content and flow. In vivo measurements demonstrate that the disc volume, fluid content, height and nucleus pressure completely recover during resting even after diurnal loading with twice longer duration (16 vs. 8 h). In view of much longer periods required for the recovery of disc height and pressure in vitro, concerns have been raised on the fluid inflow through the endplates that might be hampered by clogged blood vessels post mortem. This in silico study aimed to identify fluid-flow dependent response of discs and conditions essential to replicate in vitro and in vivo observations.An osmo-poroelastic finite element model of the human lumbar L4-L5 disc-bone unit was used. Simulating earlier in vitro experiments on bovine discs, the loading protocol started with 8 h preload at 0.06 MPa followed by 30 high/low compression loading cycles each lasting 7.5 min at 0.5/0.06 MPa, respectively. Three different endplate configurations were investigated: free in- and outflow, no inflow and closed endplates with no flow. Additionally, the preload magnitude was increased from 0.06 MPa to 0.28 MPa and 0.50 MPa, or the initial nucleus hydration was reduced from 83% to 50%.For 0.06 MPa preload, the model with no inflow best matched in vitro trends. The model with free inflow increased segment height and nucleus pressure while the model with no fluid inflow resulted in a relatively small recovery in segment height and a rather constant nucleus pressure during unloading periods.Results highlight an excessive mobile fluid content as well as a restricted fluid inflow through endplates as likely causes of the discrepancies between in vivo and in vitro studies. To replicate in vivo conditions in vitro and in silico, disc hydration level should be controlled by adequate selection of preload magnitude/period and/or mobile fluid porosity.     

Nonlinear finite element analysis of anular lesions in the L4/5 intervertebral disc

Degenerate intervertebral discs exhibit both material and structural changes. Structural defects (lesions) develop in the anulus fibrosus with age. While degeneration has been simulated in numerous previous studies, the effects of structural lesions on disc mechanics are not well known. In this study, a finite element model (FEM) of the L4/5 intervertebral disc was developed in order to study the effects of anular lesions and loss of hydrostatic pressure in the nucleus pulposus on the disc mechanics. Models were developed to simulate both healthy and degenerate discs. Degeneration was simulated with either rim, radial or circumferential anular lesions and by equating nucleus pressure to zero. The anulus fibrosus ground substance was represented as a nonlinear incompressible material using a second-order polynomial, hyperelastic strain energy equation. Hyperelastic material parameters were derived from experimentation on sheep discs. Endplates were assumed to be rigid, and annulus lamellae were assumed to be vertical in the unloaded state. Loading conditions corresponding to physiological ranges of rotational motion were applied to the models and peak rotation moments compared between models. Loss of nucleus pulposus pressure had a much greater effect on the disc mechanics than the presence of anular lesions. This indicated that the development of anular lesions alone (prior to degeneration of the nucleus) has minimal effect on disc mechanics, but that disc stiffness is significantly reduced by the loss of hydrostatic pressure in the nucleus. With the degeneration of the nucleus, the outer innervated anulus or surrounding osteo-ligamentous anatomy may therefore experience increased strains.     

持久脊柱负荷与椎间盘组织中MMP-2 表达关系的研究

目的:建立一压力可控型椎间盘退变模型,并探讨持久的脊柱负荷对椎间盘MMP-2表达的影响.方法:选用54只成年Wistar大鼠随机分为三组,分别模拟人类在站立(A组1.12N)、坐位直立(B组1.68N)、坐位前屈(C组3.08N)三种状态下椎间盘内的负荷情况,给予大鼠尾椎Co9/10椎间盘恒定压力加压,以相邻Co8/9椎间盘不加压作为对照(D组).三组分别在3、7、14天后取受压及对照椎间盘标本,进行HE染色组织学观察及免疫组织化学分析,观察椎间盘退变情况及MMP-2在椎间盘组织中的含量变化.结果:随时间与压力的增加,椎间盘组织学评分与MMP-2表达增高(P＜0.05),MMP-2表达与椎间盘退变程度成正相关(r=.870,P＜0.05).结论:持久的脊柱负荷可引起椎间盘退变及MMP-2表达增加,MMP-2可能在椎间盘退变的过程中发挥重要作用.     

Three-dimensional inhomogeneous triphasic finite-element analysis of physical signals and solute transport in human intervertebral disc under axial compression

A 3D inhomogeneous finite-element model for charged hydrated soft tissues containing charged/uncharged solutes was developed and applied to analyze the mechanical, chemical, and electrical signals within the human intervertebral disc during an axial unconfined compression. The effects of tissue properties and boundary conditions on the physical signals and the transport of fluid and solute were investigated. The numerical simulation showed that, during disc compression, the fluid pressurization and the effective (von Misses) solid stress were more pronounced in the annulus fibrosus (AF) region near the interface between AF and nucleus pulposus (NP). In NP, the distributions of the fluid pressure, effective stress, and electrical potential were more uniform than those in AF. The electrical signals were very sensitive to fixed charge density. Changes in material properties of NP (water content, fixed charge density, and modulus) affected fluid pressure, electrical potential, effective stress, and solute transport in the disc. This study is important for understanding disc biomechanics, disc nutrition, and disc mechanobiology.     

Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc

Disc herniation treated by discectomy results in a significant loss of nucleus material and disc height. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce and secrete matrix components and respond to physical stimuli such as dynamic loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In 2002 a prospective, controlled, randomised, multi-center study, EuroDISC, comparing safety and efficacy of autologous disc chondrocyte transplant, chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was initiated. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc. Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair. The clinical goals of the EuroDISC study, were to provide long-term pain relief, maintain disc height and prevent adjacent segment disease. Interim analysis was performed after 2 years; Oswestry (low back pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS score were used for the evaluation. Disc height was assessed by MRI. In the context of degenerative changes in an injury model: () autologous disc chondrocytes were expended in culture and returned to the disc by a minimally invasive procedure after 12 weeks; () disc chondrocytes remained viable after transplantation as shown by bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; () transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of Proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; () both Type II and Type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and () when the disc heights were analyzed for variance according to treatment a statistically significant-correlation between transplanting cells and retention of disc height was achieved. A clinically significant reduction of low back pain in the ADCT-treated group was shown by all three pain score systems. The median total Oswestry score was 2 in the ADCT-treated group compared with 6 in the control group. Decreases in the disability index and VAS score in ADCT-treated patients correlated strongly with the reduction of low back pain. Decreases in disc height over time were only found in the control group, and of potential significance, intervertebral discs in adjacent segments appeared to retain hydration when compared to those adjacent to levels that had undergone discectomy without cell intervention. Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.     

A magnetic resonance imaging framework for quantifying intervertebral disc deformation in vivo: Reliability and application to diurnal variations in lumbar disc shape

Low back pain is a significant socioeconomic burden in the United States and lumbar intervertebral disc degeneration is frequently implicated as a cause. The discs play an important mechanical role in the spine, yet the relationship between disc function and back pain is poorly defined. The objective of this work was to develop a technique using magnetic resonance imaging (MRI) and three-dimensional modeling to measure in vivo disc deformations. Using this method, we found that disc geometry was measurable with precision less than the in-plane dimensions of a voxel (≈100 µm, 10% of the MRI pixel size). Furthermore, there was excellent agreement between mean disc height, disc perimeter, disc volume and regional disc height measurements for multiple trials from an individual rater (standard deviation <3.1% across all measurements) and between mean height, perimeter, and volume measurements made by two independent raters (error <1.5% across all measurements). We then used this measurement system to track diurnal deformations in the L5-S1 disc in a young, healthy population (n = 8; age 24.1 ± 3.3 yrs; 2 M/6F). We measured decreases in the mean disc height (−8%) and volume (−9%) with no changes in perimeter over an eight-hour workday. We found that the largest height losses occurred in the posterior (−13%) and posterior-lateral (−14%) regions adjacent to the outer annulus fibrosus. Diurnal annulus fibrosus (AF) strains induced by posterior and posterior-lateral height loss may increase the risk for posterior disc herniation or posterior AF tears. These preliminary findings lay a foundation for determining how deviations from normal deformations may contribute to back pain.     

Neural arch load-bearing in old and degenerated spines

We validate a technique for measuring neural arch load-bearing in cadaveric spines, and use it to test the hypothesis that such load-bearing rises to high levels in old and degenerated spines. Fifty-nine cadaveric lumbar motion segments, aged 19-92 yr, were subjected to compressive creep loading to reduce intervertebral disc water content and height to in vivo levels. The distribution of compressive "stress" within the disc was then measured by pulling a miniature pressure transducer, side-mounted in a 1.3mm-diameter needle, along its mid-sagittal diameter. During these measurements, the motion segment was subjected to a compressive load of 2 kN, and positioned in 2 degrees of extension to simulate erect standing. Measurements of compressive "stress" were integrated over disc area, and this force subtracted from the applied 2 kN to give the force resisted by the neural arch. An empirical calibration factor was applied to normalise results from each disc to values obtained under conditions when all of the compressive force could be assumed to pass through the disc. Disc degeneration was graded macroscopically on a scale of 1-4. Validation tests showed that calculated values of disc loading were proportional to actual applied load (r(2)>0.96) and predicted it with errors of 2-8%. Neural arch load-bearing in non-degenerated specimens was generally less than 20%, but averaged 49% for specimens aged over 70 yr. Multiple regression showed that neural arch load bearing (%)=14.4 x disc degeneration score+0.46 x age-35. These results indicate a substantial shift in vertebral load-bearing with increasing age and degeneration.     

3D finite element analysis of nutrient distributions and cell viability in the intervertebral disc: effects of deformation and degeneration

The intervertebral disc (IVD) receives important nutrients, such as glucose, from surrounding blood vessels. Poor nutritional supply is believed to play a key role in disc degeneration. Several investigators have presented finite element models of the IVD to investigate disc nutrition; however, none has predicted nutrient levels and cell viability in the disc with a realistic 3D geometry and tissue properties coupled to mechanical deformation. Understanding how degeneration and loading affect nutrition and cell viability is necessary for elucidating the mechanisms of disc degeneration and low back pain. The objective of this study was to analyze the effects of disc degeneration and static deformation on glucose distributions and cell viability in the IVD using finite element analysis. A realistic 3D finite element model of the IVD was developed based on mechano-electrochemical mixture theory. In the model, the cellular metabolic activities and viability were related to nutrient concentrations, and transport properties of nutrients were dependent on tissue deformation. The effects of disc degeneration and mechanical compression on glucose concentrations and cell density distributions in the IVD were investigated. To examine effects of disc degeneration, tissue properties were altered to reflect those of degenerated tissue, including reduced water content, fixed charge density, height, and endplate permeability. Two mechanical loading conditions were also investigated: a reference (undeformed) case and a 10% static deformation case. In general, nutrient levels decreased moving away from the nutritional supply at the disc periphery. Minimum glucose levels were at the interface between the nucleus and annulus regions of the disc. Deformation caused a 6.2% decrease in the minimum glucose concentration in the normal IVD, while degeneration resulted in an 80% decrease. Although cell density was not affected in the undeformed normal disc, there was a decrease in cell viability in the degenerated case, in which averaged cell density fell 11% compared with the normal case. This effect was further exacerbated by deformation of the degenerated IVD. Both deformation and disc degeneration altered the glucose distribution in the IVD. For the degenerated case, glucose levels fell below levels necessary for maintaining cell viability, and cell density decreased. This study provides important insight into nutrition-related mechanisms of disc degeneration. Moreover, our model may serve as a powerful tool in the development of new treatments for low back pain.     

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

In this study, the authors explored the effect of human mesenchymal stem cell (MSC) implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat. A unique rat coccygeal model was used to investigate the effects of transplanting human MSCs and to examine MSC survival in degenerative discs. MSC implantations into rat coccygeal IVDs were performed at 2 weeks post-injury. Radiologic and histologic evaluations were performed at 2, 4, 6, and 8 weeks post-injury. MSC-injected segments (TS) retained disc height and signal intensity, but injured non-injected segment (IS) progressively lost disc height. Pathological results revealed that the TS group showed relative restoration of the inner annulus structure; however, the IS group showed destruction of the inner annulus structure. Immunohistochemical staining using Anti-Human Nucleic Antibody (#MAB1281 Chemicon) revealed positive staining in the TS group at 2 weeks post-transplantation (4 weeks post-injury). This study shows that human MSCs survive for 2 weeks after transplantation into the IVDs of rats, and that MSCs increased the heights and signal intensities of intervertebral disc.