TNF?-stimulated gene product (TSG-6) and its binding protein, I?I, in the human intervertebral disc: new molecules for the disc

Roberts, S.; Evans, Helena; Menage, J.; Urban, Jill; Bayliss, Michael T.; Eisenstein, Stephen M.; Rugg, Marylin S.; Milner, Caroline M.; Griffin, Síle M.; Day, Anthony J.

doi:10.1007/s00586-004-0798-x

Cited by 33 publications

(19 citation statements)

References 34 publications

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“…Although cells of most human discs appear to be able to produce cytokines and inflammatory mediators (e.g., interleukins, tumor necrosis factor [TNF]-α, monocyte chemoattractant protein-1, and TNF-α stimulating gene [TSG-6]), they are more com-monly found in herniated discs compared with normal discs (Fig. 2, G) 25 . These samples are also more highly innervated than normal discs, with 80% having nerves present 24 .…”

Section: Herniated Intervertebral Discmentioning

confidence: 99%

Histology and Pathology of the Human Intervertebral Disc

Roberts¹,

Evans²,

Trivedi³

et al. 2006

Journal of Bone and Joint Surgery

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The intervertebral disc is a highly organized matrix laid down by relatively few cells in a specific manner. The central gelatinous nucleus pulposus is contained within the more collagenous anulus fibrosus laterally and the cartilage end plates inferiorly and superiorly. The anulus consists of concentric rings or lamellae, with fibers in the outer lamellae continuing into the longitudinal ligaments and vertebral bodies. This arrangement allows the discs to facilitate movement and flexibility within what would be an otherwise rigid spine. At birth, the human disc has some vascular supply within both the cartilage end plates and the anulus fibrosus, but these vessels soon recede, leaving the disc with little direct blood supply in the healthy adult. With increasing age, water is lost from the matrix, and the proteoglycan content also changes and diminishes. The disc-particularly the nucleus-becomes less gelatinous and more fibrous, and cracks and fissures eventually form. More blood vessels begin to grow into the disc from the outer areas of the anulus. There is an increase in cell proliferation and formation of cell clusters as well as an increase in cell death. The cartilage end plate undergoes thinning, altered cell density, formation of fissures, and sclerosis of the subchondral bone. These changes are similar to those seen in degenerative disc disease, causing discussion as to whether aging and degeneration are separate processes or the same process occurring over a different timescale. Additional disorders involving the intervertebral disc can demonstrate other changes in morphology. Discs from patients with spinal deformities such as scoliosis have ectopic calcification in the cartilage end plate and sometimes in the disc itself. Cells in these discs and cells from patients with spondylolisthesis have been found to have very long cell processes. Cells in herniated discs appear to have a higher degree of cellular senescence than cells in nonherniated discs and produce a greater abundance of matrix metalloproteinases. The role that abnormalities play in the etiopathogenesis of different disorders is not always clear. Disorders may be caused by a genetic predisposition or a tissue response to an insult or altered mechanical environment. Whatever the initial cause, a change in the morphology of the tissue is likely to alter the physiologic and mechanical functioning of the tissue.

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Section: Herniated Intervertebral Discmentioning

confidence: 99%

Histology and Pathology of the Human Intervertebral Disc

Roberts¹,

Evans²,

Trivedi³

et al. 2006

Journal of Bone and Joint Surgery

Self Cite

566

500

View full text Add to dashboard Cite

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“…If the symptoms are persistent, cause progressive deformity or neurologic compromise, surgery in the form of disc replacement or spinal fusion is considered [48] . Growth factors, inflammatory cytokine antagonists and intracellular regulatory proteins are among the factors which have been demonstrated to result in encouraging regeneration of nucleus pulposus cells in vitro and in vivo [49][50][51][52][53] . The utility of these therapies in humans may be limited due to the rapid in vivo degeneration of the molecules used for the treatment.…”

Section: Disc Regenerationmentioning

confidence: 99%

Stem cells for spine surgery

Schroeder

Kueper

Kaplan

et al. 2015

WJSC

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In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion.

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“…collected 58 herniated discs from 54 patients, and found TSG-6 and its binding protein, IαI, to be present in nearly all discs. [62] While the precise function of TSG-6, IαI, and their interaction is not fully known, future research is merited to study how these molecules can be exploited in anticatabolic treatment approaches.…”

Section: Enhancing Disc Regeneration By Slowing the Degenerative Processmentioning

confidence: 99%

Molecular and genetic advances in the regeneration of the intervertebral disc

Maerz

Herkowitz²,

Baker³

2013

Surg Neurol Int

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Background:Owing to the debilitating nature of degenerative disc disease (DDD) and other spine pathologies, significant research has been performed with the goal of healing or regenerating the intervertebral disc (IVD). Structural complexity, coupled with low vascularity and cellularity, make IVD regeneration an extremely challenging task.Methods:Tissue engineering-based strategies utilize three components to enhance tissue regeneration; scaffold materials to guide cell growth, biomolecules to enhance cell migration and differentiation, and cells (autologous, or allogeneic) to initiate the process of tissue formation. Significant advances in IVD regeneration have been made utilizing these tissue engineering strategies.Results:The current literature demonstrates that members of the transforming growth factor beta (TGF-β) superfamily are efficacious in the regeneration of an anabolic response in the IVD and to facilitate chondrogenic differentiation. Gene therapy, though thwarted by safety concerns and the risk of ectopic transfection, has significant potential for a targeted and sustained regenerative response. Stem cells in combination with injectable, biocompatible, and biodegradable scaffolds in the form of hydrogels can differentiate into de novo IVD tissue and facilitate regeneration of the existing matrix. Therapies that address both anabolism and the inherent catabolic state of the IVD using either direct inhibitors or broad-spectrum inhibitors show extensive promise.Conclusion:This review article summarizes the genetic and molecular advances that promise to play an integral role in the development of new strategies to combat DDD and promote healing of injured discs.

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TNF?-stimulated gene product (TSG-6) and its binding protein, I?I, in the human intervertebral disc: new molecules for the disc

Cited by 33 publications

References 34 publications

Histology and Pathology of the Human Intervertebral Disc

Histology and Pathology of the Human Intervertebral Disc

Stem cells for spine surgery

Molecular and genetic advances in the regeneration of the intervertebral disc

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