GENE THERAPY: A NOVEL APPROACH TO TREATMENT OF THE DEGENERATION OF INTERVERTEBRAL DISCS

2002 ◽  
Vol 06 (03n04) ◽  
pp. 181-187 ◽  
Author(s):  
Jiangwei Tan ◽  
Yougu Hu
Keyword(s):  
Gene Therapy ◽  
Back Pain ◽  
Disc Degeneration ◽  
Deep Understanding ◽  
Intervertebral Discs ◽  
Research Field ◽  
Clinical Approach ◽  
Novel Approach ◽  
Physiology And Biochemistry ◽  
Lowback Pain

The degeneration of intervertebral discs is one of the pathophysiological causes of lowback pain which has been seriously disturbing human health at the present, No clinical approach can provide prophylaxis or treatment for disc degeneration. But people are now thinking about gene transfer for the prevention of disc degeneration to reduce the incidence of back pain. This idea originated from the development of molecular biology; the deep understanding of the physiology and biochemistry of the intervertebral discs, and the growing scope of gene therapy. The increasing publications on gene therapy for disc degeneration have shown us the future of this research field, and revealed possible difficulties in the process of the study. This article focuses on several important aspects of gene therapy for disc degeneration.

scholarly journals Relationship between Endplate Defects, Modic Change, Disc Degeneration, and Facet Joint Degeneration in Patients with Low Back Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Bin Lv ◽  
Jishan Yuan ◽  
Hua Ding ◽  
Bowen Wan ◽  
Qinyi Jiang ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Disc Degeneration ◽  
Facet Joint ◽  
Degenerative Change ◽  
Intervertebral Discs ◽  
Low Back ◽  
Joint Degeneration ◽  
Facet Joint Degeneration ◽  
Before And After

Purpose. The endplate defects (EDs), Modic changes (MCs), disc degeneration (DD), facet orientation (FO), and facet tropism (FT) were demonstrated to be related to the low back pain (LBP). The aim of this study was to investigate possible correlations between them. Methods. 75 patients were reviewed to evaluate the degenerative change in vertebral bodies (EDs and MCs), intervertebral discs (DD), and facet joint degeneration (FO and FT). All patients were categorized into four groups based on the grade of EDs. Clinical outcomes were evaluated with the visual analog scale (VAS) and Oswestry disability index (ODI) before and after surgery. Results. There was no difference between the four groups in baseline characteristics except for gender and weight. FT is positively correlated with FO. The same rule exists between EDs, the size of MCs II, FO (left) and FO (right), and VAS and ODI. The grade of EDs is positively correlated with the grade of DD. L4-L5 can bear more load than other levels; thus, the grade of EDs is higher than that of other lumbar levels. The preoperative LBP was relieved in all groups in varying degrees. The change of pain and dysfunction is inversely proportional to the grade of EDs in the general trend. Conclusion. The relationship between weight, gender, and disc degeneration provided a mechanism by which increasing weight can predispose to DD. Different grades of EDs had different effects on patients with LBP. There was a significant correlation between EDs, MCs II, DD, FT, and FO.

scholarly journals Disordered Mechanical Stress and Tissue Engineering Therapies in Intervertebral Disc Degeneration

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1151 ◽  
Author(s):  
Runze Zhao ◽  
Wanqian Liu ◽  
Tingting Xia ◽  
Li Yang
Keyword(s):  
Tissue Engineering ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Mechanical Stress ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Body Motion

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies.

scholarly journals Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Matthew Mannarino ◽  
Hosni Cherif ◽  
Li Li ◽  
Kai Sheng ◽  
Oded Rabau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Back Pain ◽  
Protein Expression ◽  
Disc Degeneration ◽  
Cell Senescence ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Synthesis ◽  
Gene And Protein Expression ◽  
Pain Patients ◽  
In Cells

Abstract Background There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. Methods Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. Conclusions Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

The association of combination of disc degeneration, end plate signal change, and Schmorl node with low back pain in a large population study: the Wakayama Spine Study

2015 ◽  
Vol 15 (4) ◽  
pp. 622-628 ◽  
Author(s):  
Masatoshi Teraguchi ◽  
Noriko Yoshimura ◽  
Hiroshi Hashizume ◽  
Shigeyuki Muraki ◽  
Hiroshi Yamada ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Disc Degeneration ◽  
Population Study ◽  
Large Population ◽  
Low Back ◽  
End Plate ◽  
Signal Change

scholarly journals Low Back Pain: The Potential Contribution of Supraspinal Motor Control and Proprioception

2018 ◽  
Vol 25 (6) ◽  
pp. 583-596 ◽  
Author(s):  
Michael Lukas Meier ◽  
Andrea Vrana ◽  
Petra Schweinhardt
Keyword(s):  
Low Back Pain ◽  
Motor Control ◽  
Back Pain ◽  
Control Strategies ◽  
Intervertebral Discs ◽  
Cortical Reorganization ◽  
Potential Contribution ◽  
Low Back ◽  
Output Side

Motor control, which relies on constant communication between motor and sensory systems, is crucial for spine posture, stability and movement. Adaptions of motor control occur in low back pain (LBP) while different motor adaption strategies exist across individuals, probably to reduce LBP and risk of injury. However, in some individuals with LBP, adapted motor control strategies might have long-term consequences, such as increased spinal loading that has been linked with degeneration of intervertebral discs and other tissues, potentially maintaining recurrent or chronic LBP. Factors contributing to motor control adaptations in LBP have been extensively studied on the motor output side, but less attention has been paid to changes in sensory input, specifically proprioception. Furthermore, motor cortex reorganization has been linked with chronic and recurrent LBP, but underlying factors are poorly understood. Here, we review current research on behavioral and neural effects of motor control adaptions in LBP. We conclude that back pain-induced disrupted or reduced proprioceptive signaling likely plays a pivotal role in driving long-term changes in the top-down control of the motor system via motor and sensory cortical reorganization. In the outlook of this review, we explore whether motor control adaptations are also important for other (musculoskeletal) pain conditions.

scholarly journals Stem Cell Delivery with Polymer Hydrogel for Treatment of Intervertebral Disc Degeneration: From 3D Culture to Design of the Delivery Device for Minimally Invasive Therapy

2016 ◽  
Vol 25 (12) ◽  
pp. 2213-2220 ◽  
Author(s):  
Deepak Kumar ◽  
Alex Lyness ◽  
Irini Gerges ◽  
Christina Lenardi ◽  
Nicholas R. Forsyth ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Disc Degeneration ◽  
Mechanical Strain ◽  
3D Culture ◽  
Human Mesenchymal Stem Cells ◽  
Intervertebral Discs ◽  
Delivery Device ◽  
Polymer Hydrogel ◽  
Uv Curable ◽  
Stem Cell Delivery

Nucleus pulposus (NP) tissue damage can induce detrimental mechanical strain on the biomechanical performance of intervertebral discs (IVDs), causing subsequent disc degeneration. A novel, photocurable, injectable, synthetic polymer hydrogel (pHEMA-co-APMA grafted with PAA) has already demonstrated success in encapsulating and differentiating human mesenchymal stem cells (hMSCs) toward an NP phenotype during hypoxic conditions. After demonstration of promising results in our previous work, in this study we have further investigated the inclusion of mechanical stimulation and its impact on hMSC differentiation toward an NP phenotype through the characterization of matrix markers such as SOX-9, aggrecan, and collagen II. Furthermore, investigations were undertaken in order to approximate delivery parameters for an injection delivery device, which could be used to transport hMSCs suspended in hydrogel into the IVD. hMSC-laden hydrogel solutions were injected through various needle gauge sizes in order to determine its impact on postinjection cell viability and IVD tissue penetration. Interpretation of these data informed the design of a potential minimally invasive injection device, which could successfully inject hMSCs encapsulated in a UV-curable polymer into NP, prior to photo-cross-linking in situ.

scholarly journals Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

2012 ◽  
Vol 2 (1) ◽  
pp. 6 ◽  
Author(s):  
Marie Klauser ◽  
Franck Forterre ◽  
Marcus Doherr ◽  
Andreas Zurbriggen ◽  
David Spreng ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Intervertebral Discs ◽  
Discogenic Pain ◽  
Age Related ◽  
Chondroid Metaplasia ◽  
Related Increase

Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP) was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose) polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose) polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

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