| 1. |
- Barreto Henriksson, Helena, et al.
(författare)
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Identification of Cell Proliferation Zones, Progenitor Cells and a Potential Stem Cell Niche in the Intervertebral Disc Region: A Study in Four Species.
- 2009
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Ingår i: SPINE. - 0362-2436. ; 34:21, s. 2278-2287
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN.: Descriptive experimental study in 4 different mammals. OBJECTIVE.: To investigate cell proliferation/regeneration and localize stem cells/progenitor cells within the intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA.: Disc degeneration (DD) is believed to play a major role in patients with chronic lumbar pain. Lately, biologic treatment options for DD have gained increasing interest. Normal regeneration processes within the IVD and have previously been sparsely described and therefore it is of great interest to increase the knowledge about these processes. METHODS.: Detection of cell proliferations zones and label-retaining cells were done by in vivo 5-bromo-2-deoxyuridine (BrdU) labeling in 18 rabbits, killed after 4, 6, 10, 14, 28, or 56 days. Results were visualized with immunohistochemistry and fluorescence/confocal microscopy. Localization of progenitor cell were further investigated by immunohistochemistry using antibodies towards Notch1, Delta4, Jagged1, C-KIT, KI67, and Stro-1 in normal IVD from rabbits (n = 3), rats (n = 2), minipigs (n = 2), and in human degenerated IVD (n = 4). Further, flowcytometry analysis using progenitor markers were performed on additional human IVD cells (n = 3). RESULTS.: BrdU positive cells were found in comparable numbers at early and late time points in most regions of the anulus fibrosus (AF) and nucleus pulposus demonstrating slow ongoing cell proliferation. In the AF border to ligament zone (AFo) and the perichondriumregion (P) a stem cell niche-like pattern was determined (a high number of BrdU positive cells at early time points vs. only a few label retaining cells at later time points). In normal and DD tissue from the 4 investigated species progenitor cell markers were detected. CONCLUSION.: The IVD is a tissue with ongoing slow cell proliferation both in the AF and the nucleus pulposus. The stem cell niche pattern detected in AFo and P can be suggested to play a role for IVD morphology and function. These findings may be of importance for the development of biologic treatment strategies. PMID: 19755937 [PubMed - as supplied by publisher]
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| 2. |
- Barreto Henriksson, Helena, et al.
(författare)
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Support of Concept that Migrating Progenitor Cells from Stem Cell Niches Contribute to Normal Regeneration of the Adult Mammal Intervertebral Disc: A Descriptive study in the New Zeeland white Rabbit.
- 2012
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 37:9, s. 722-732
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Study Design. Descriptive experimental study performed in rabbits of two age groups.Objective. To study and investigate presence of prechondrocytic cells and cell migration routes in the IVD region, to gain knowledge about the normal IVD regeneration pattern.Summary of Background Data. Disc degeneration is believed to play a major role in patients with chronic lumbar pain. Regeneration processes and cell migration within the intervertebral disc (IVD) have been sparsely described. Therefore it is of interest to increase knowledge of these processes in order to understand pathological conditions of the IVD.Methods. 5-bromo-2-deoxyuridine (BrdU) in vivo labelling was performed in two groups of rabbits, 3 and 9 months old at the beginning of the experiment, in total 27 rabbits. BrdU is incorporated into DNA during mitosis and then it is gradually diluted with each cell division until it finally disappears. Incorporation of BrdU was then visualized by immunohistochemistry (IHC) at different time points providing cell division pattern and presence of slow-cycling cells in the IVD region. IVD tissue was investigated by IHC for: Growth- and differentiation-factor-5 (GDF5), SOX9 (chondrogenic lineage markers), SNAIL homolog1 (SNAI1), SNAIL homolog2 (SLUG)(migration markers) and β1-INTEGRIN (cellular adhesion marker). In addition, GDF5, SOX9 and BMPRIB expression were investigated on genetic level.Results. BrdU+ cells were observed in early time points in the IVD niche, adjacent to the epiphyseal plate, at later time points mainly in outer region of the annulus fibrosus (AF) for both age groups of rabbits, indicating a gradual migration of cells. The presence of SLUG, SNAI1, GDF5, SOX9 and β1-INTEGRIN were found in same regions.Conclusion. The results suggest a cellular migration route from the IVD stem cell niche toward the AF and the inner parts of the IVD. These findings may be of importance for understanding IVD regenerative mechanisms and for future development of biological treatment strategies.
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| 3. |
- Hermansen, E., et al.
(författare)
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Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial
- 2023
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436. ; 48:10, s. 688-694
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Tidskriftsartikel (refereegranskat)abstract
- Study Design.Prospective cohort study. Objective.The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. Summary of Background Data.There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. Materials and Methods.All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2).The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. Results.At baseline, the mean DSCA in the whole cohort was 51.1 mm(2) (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm(2) (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was -22.0 (95% CI: -25.6 to -18), and in the quintile with the lowest DSCA the Oswestry disability index change was -18.9 (95% CI: -22.4 to -15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. Conclusion.Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery.
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| 4. |
- Hutchins, John, et al.
(författare)
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Evaluation of Cervical Vertebral Motion and Foraminal Changes During the Spurling Test Using Zero Echo Time Magnetic Resonance Imaging and Computed Tomography-Based Micromotion Analysis
- 2024
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Ingår i: SPINE. - 0362-2436 .- 1528-1159. ; 49:14
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Tidskriftsartikel (refereegranskat)abstract
- Study Design.Clinical experimental diagnostic study.Objective.The objective of the study was to investigate cervical spine dynamics including changes in the cervical foramina in patients experiencing intermittent arm radiculopathy.Background.Cervical foraminal stenosis is a frequent cause of radicular arm pain. The Spurling test, while specific, lacks the precision to identify symptomatic nerve roots. The relationship among vertebral motion, foraminal changes, and radiculopathy during a Spurling test remains underexplored.Patients and Methods.Ten patients with positive Spurling tests and magnetic resonance imaging (MRI) confirmed 1 or 2-level cervical foraminal stenosis were scanned using the Dynamic MRI Compression System enabling a simulated Spurling test inside the MRI gantry of a 3T MRI scanner with a dedicated neck coil. First, a relaxed image acquisition was undertaken, followed by slowly applying the Spurling test until the patient reported aggravation of radiculopathy or discomfort, where the next image series was taken. Zero echo time MRI was employed to obtain computed tomography (CT)-like images. The images were thereafter analyzed using the Sectra (R) CT-based Micromotion Analysis software for motion analysis.Results.The C4/C5 level exhibited the most significant movements both in translation and rotation, with less movements observed in C5 to C6 and C6 to C7 levels. No uniform pattern emerged that differentiated suspected stenotic levels from nonsuspected levels. Despite relatively small vertebral movements, 9/10 of patients reported arm pain during provocation, indicating extremely narrow margins of tolerance.Conclusion.This study demonstrates the utility of zero echo time MRI and CT-based Micromotion Analysis in detecting subtle yet clinically relevant vertebral motions influencing the foramina in the cervical spine during the Spurling maneuver. These findings could lead to a better understanding and potentially improved diagnostic strategies for cervical foraminal stenosis, although further research with a larger cohort is necessary to confirm these results.
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| 5. |
- Larsson, Karin, 1955, et al.
(författare)
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Effects of Intervertebral Disc Cells on Neurite Outgrowth From Dorsal Root Ganglion Explants in Culture
- 2011
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Ingår i: Spine (Phila Pa 1976). - 0362-2436. ; 36:8, s. 600-6
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN.: An experimental study investigating the effect of disc cells on neurite outgrowth in a rat dorsal root ganglion (DRG) culture system. OBJECTIVE.: To examine the effects of the 2 nucleus pulposus (NP) cell populations, notochordal cells (NC) and chondrocyte-like cells (CC) on neurite outgrowth from DRGs. SUMMARY OF BACKGROUND DATA.: NP consists of at least 2 cell populations, NC and CC. The cells in NP have been shown to be responsible for negative effects on neurite outgrowth in vitro and on nerve tissue in vivo. It is unknown whether 1 cell type or combinations of the 2 cell types are responsible for the reported effects. METHODS.: A total of 939 DRGs from newborn Sprague Dawley rats were harvested and placed in culture dishes. After 24 hours, the neurite outgrowth was measured. NP was harvested from tail discs of adult rats and the NP cells were separated into 2 populations, NC and CC. The cell populations were applied to the DRG culture in different cell concentrations and combinations, and compared to medium. After 24 hours of exposure, the neurite outgrowth was reassessed and expressed as the ratio between the outgrowth at 48 and 24 hours culture. RESULTS.: NC in intermediate and high concentration and CC in high concentration induced a significant inhibition of the neurite outgrowth compared to culture medium. Further, one of the combinations (low NC and high CC concentration) resulted in a significant inhibition of the neurite outgrowth. CONCLUSION.: The present study demonstrated negative effects of NP cells on nerve tissue culture explants. The combination of low NC and high CC concentrations may mimic the situation in humans, where we have an increased proportion of chondrocyte-like cells with age. The results from this study may provide a biologic explanation for the large variation of symptoms in disc herniation patients despite similar mechanical influence on nerve tissue.
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| 6. |
- Rönnberg, Katarina, 1969, et al.
(författare)
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Patients' satisfaction with provided care/information and expectations on clinical outcome after lumbar disc herniation surgery
- 2007
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 32:2, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN. A prospective study of patients undergoing lumbar disc herniation surgery. OBJECTIVES. To assess patients' satisfaction with care/preoperative information, if expectations on surgical results and ability to return to work are related to baseline characteristics, and/or can predict self-reported outcome. Self-reported outcome was compared with objective outcome. SUMMARY OF BACKGROUND DATA. Patients' expectations on treatment results have been discussed as a predictive factor for postoperative outcome and satisfaction demonstrated to be directly related to patient expectations. METHODS. The study includes 148 patients, 46% women, mean age 40 (range 18-66). Before and 2 years after surgery, questionnaires about given information/care, expected/present work ability, and expectations on/obtained improvement of physical functions/symptoms (leg and back pain, sensibility, and muscle function) were filled in. The visual analog scale leg pain, Zung Depression Scale, and Oswestry Disability Index were used as baseline characteristics. At 2-year follow-up, self-reported and objective outcome was assessed. RESULTS. Satisfaction with given information/care were reported by 46% and 82%, respectively. Zung Depression Scale related to expectations on leg pain recovery (P = 0.022), work ability (P = 0.046), and satisfaction with given information (P = 0.031). Patients who expected to return (76%) and not return (24%) to work, returned in 78% and 26%, respectively (P = 0.021). A high agreement between self-reported outcome and objective outcome were found (P < 0.001). CONCLUSIONS. Patients undergoing lumbar disc herniation surgery are mostly satisfied with provided care before and after surgery, however, less satisfied with information provided. Further, patients with preoperative positive expectations on work return and realistic expectations on pain and physical recovery have a greater chance to be satisfied with the surgical results. © 2007 Lippincott Williams & Wilkins, Inc.
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| 7. |
- Suzuki, Nobuyuki, 1971, et al.
(författare)
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Physical exercise affects cell proliferation in lumbar intervertebral disc regions in rats
- 2012
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Ingår i: Spine. - 0362-2436. ; 37:17, s. 1440-1447
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Descriptive experimental study.Objective. The aim of this study was to investigate the effect of exercise on cell proliferation in different areas of the IVD and recruitment of cells possibly active in regeneration of normal rat lumbar IVDs.Summary of Background Data. Little is known about the effects of physical exercise on lumbar intervertebral disc (IVD) tissue. Recently, stem cell niches in the perichondrium area of the IVD were identified and cells in these niches have been suggested to be involved in the normal regeneration of the IVD.Methods. Thirty Sprague-Dawley rats were exposed to 5-bromo-2-deoxyuridine (BrdU) diluted in the drinking water during 14 days. Fifteen rats ran on a treadmill daily for 50 min/day, 5 days/week (exercise group) and 15 non-exercised rats served as controls. Immunohistochemical analyses (anti-BrdU antibody) were performed at 9, 14, 28, 56 and 105 days after the start of the exercise protocol. BrdU positive cells were counted in the stem cell niche area (SN), peripheral region of epiphyseal cartilage area (pEC), the annulus fibrous outer and inner area (AFo and AFi). Data were analyzed by two-way ANOVA (significance level; p<0.05).Results. The BrdU positive cell numbers in the SN and AFo region were increased in discs from the exercising group on days 14 (p<0.01) and 105 (p<0.05) and at day 14 (p<0.01) in the pEC region as compared to controls.Conclusions. Physical exercise was shown to have positive effects on cell proliferation in intervertebral discs with involvement of various disc regions, indicating a differential response by disc tissue to exercise depending on anatomical location and tissue characteristics.
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| 8. |
- Torén, Leif, et al.
(författare)
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Different Load-Induced Alterations in Intervertebral Discs Between Low Back Pain Patients and Controls
- 2024
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Ingår i: SPINE. - 0362-2436 .- 1528-1159. ; 49:15
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Prospective cohort study. Objective. Investigate load-induced effects in lumbar intervertebral discs (IVDs) and differences between low back pain (LBP) patients and controls. Summary of Background Data.T2-map values, obtained from quantitative MRI sequences, reflect IVD tissue composition and integrity. Feasibility studies with T2-mapping indicate different load-induced effects in entire IVDs and posterior IVD parts between LBP patients and controls. Larger studies are required to confirm these findings and increase the understanding of specific characteristics distinguishing IVD changes in LBP patients compared with controls. Materials and Methods. Lumbar IVDs of 178 patients (mean age: 43.8 yr; range: 20-60 yr) with >3 months of LBP and 74 controls (mean age: 40.3 yr; range: 20-60 yr) were imaged with T2-map sequence in a 3T scanner in supine position without axial load, immediately followed by a repeated examination, using the same sequence, with axial load. On both examinations, mean T2-map values were obtained from entire IVDs and from central/posterior IVD parts on the three midsagittal slices in 855 patient IVDs and 366 control IVDs. Load-induced effect was compared with Fold-change ratio and adjusted for IVD-degeneration grade. Results. Loading induced an increase in T2-map values in both patients and controls. Excluding most extreme values, the ranges varied between -15% and +35% in patients and -11% and +36% in controls (first to 99th percentile). Compared with controls, the T2-map value increase in patients was 2% smaller in entire IVDs (Fold-change: 0.98, P=0.031), and for central and posterior IVD parts 3% (Fold-change: 0.98, P=0.005), respectively, 2% (Fold-change: 0.9, P=0.015) smaller. Conclusions. This quantitative study confirmed diverse load-induced behaviors between LBP patients and controls, suggesting deviant biomechanical characteristics between IVDs in patients and controls not only attributed to the global grade of degeneration. These findings are an important step in the continuous work of identifying specific IVD phenotypes for LBP patients. Level of Evidence.Level II.
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| 9. |
- Torén, Leif, et al.
(författare)
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MRI During Spinal Loading Reveals Intervertebral Disc Behavior Corresponding to Discogram Findings of Annular Fissures and Pain Provocation. : Torén L, Lagerstrand K, Waldenberg C, Brisby H, Hebelka H.
- 2020
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 45:22
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Tidskriftsartikel (refereegranskat)abstract
- Study design: Retrospective analysis of prospectively collected data. Objective: The aim of this study was to investigate whether spinal loading, depicted with magnetic resonance imaging (MRI), induces regional intervertebral disc (IVD) differences associated with presence and width of annular fissure and induced pain at discography. Summary of background data: Annular fissures play a role in low back pain (LBP) but cannot be accurately characterized with conventional MRI. Recently, annular fissures were suggested to influence different load-induced IVD behavior during MRI when comparing LBP-patients and controls. Thus, the loading effect could characterize behavior related to annular fissures noninvasively with MRI. Methods: Lumbar spines of 30 LBP-patients were investigated with MRI with and without loading, discography and CT. Five IVD regions were outlined on sagittal MRI images. Difference in normalized signal intensity (SI) with and without loading was calculated for each region. Eighty-three CT-discograms were graded regarding presence and width of fissures. Discograms were classified as pain-positive if a concordant pain response was obtained at a pressure <50 psi. Results: Comparing IVDs with outer fissures with IVDs without fissures, loading induced different behavior in the two ventral regions and in the posterior region. Higher SI increase in the central region was induced in IVDs with narrower fissures compared to IVDs with wider fissures. In the group of pain-negative discograms, a SI decrease was induced in the dorsal region whereas lack of such in the pain-positive group. Conclusion: The spinal loading-effect, depicted with MRI, reveals different regional behaviors between IVDs with outer fissures compared to those without, and between IVDs with narrow and broad fissures, as well as within posterior annulus between pain-positive and pain-negative discograms. Findings are of importance for future attempts to uncover phenotypes of painful IVDs.
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