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Orthopaedic Surgery Jul 2022Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which... (Review)
Review
Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which contribute to high social and economic costs. IDD results from many factors, including genetic factors, aging, mechanical injury, malnutrition, and so on. The pathological changes of IDD are mainly composed of the senescence and apoptosis of nucleus pulposus cells (NPCs), the progressive degeneration of extracellular matrix (ECM), the fibrosis of annulus fibrosus (AF), and the inflammatory response. At present, IDD can be treated by conservative treatment and surgical treatment based on patients' symptoms. However, all of these can only release the pain but cannot reverse IDD and reconstruct the mechanical function of the spine. The latest research is moving towards the field of biotherapy. Mesenchymal stem cells (MSCs) are regard as the potential therapy of IDD because of their ability to self-renew and differentiate into a variety of tissues. Moreover, the non-coding RNAs (ncRNAs) are found to regulate many vital processes in IDD. There have been many successes in the in vitro and animal studies of using biotherapy to treat IDD, but how to transform the experimental data to real therapy which can apply to humans is still a challenge. This article mainly reviews the treatment strategies and research progress of IDD and indicates that there are many problems that need to be solved if the new biotherapy is to be applied to clinical treatment of IDD. This will provide reference and guidance for clinical treatment and research direction of IDD.
Topics: Animals; Annulus Fibrosus; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Mesenchymal Stem Cells; Nucleus Pulposus
PubMed: 35486489
DOI: 10.1111/os.13254 -
Biomaterials Jun 2017The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to... (Review)
Review
The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.
Topics: Animals; Biocompatible Materials; Humans; Intervertebral Disc; Regeneration; Tissue Engineering; Wound Healing
PubMed: 28324865
DOI: 10.1016/j.biomaterials.2017.03.013 -
International Journal of Molecular... Jun 2022Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging,... (Review)
Review
Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging, mechanical trauma, lifestyle factors, and certain genetic abnormalities, leads to loss of nucleus pulposus, alteration in the composition of the extracellular matrix, excessive oxidative stress, and inflammation in the intervertebral disc. Pharmacological and surgical interventions are considered a boon for the treatment of IVDD, but the effectiveness of those strategies is limited. Mesenchymal stem cells (MSCs) have recently emerged as a possible promising regenerative therapy for IVDD due to their paracrine effect, restoration of the degenerated cells, and capacity for differentiation into disc cells. Recent investigations have shown that the pleiotropic effect of MSCs is not related to differentiation capacity but is mediated by the secretion of soluble paracrine factors. Early studies have demonstrated that MSC-derived exosomes have therapeutic potential for treating IVDD by promoting cell proliferation, tissue regeneration, modulation of the inflammatory response, and reduced apoptosis. This paper highlights the current state of MSC-derived exosomes in the field of treatment of IVDD with further possible future developments, applications, and challenges.
Topics: Exosomes; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Mesenchymal Stem Cells; Nucleus Pulposus
PubMed: 35806304
DOI: 10.3390/ijms23137306 -
Theranostics 2021Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current... (Review)
Review
Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent , and pre-clinical studies.
Topics: Animals; Apoptosis; Humans; Inflammation; Intervertebral Disc; Intervertebral Disc Degeneration; Oxidative Stress; Regeneration
PubMed: 33391459
DOI: 10.7150/thno.48987 -
The New England Journal of Medicine Jul 1994The relation between abnormalities in the lumbar spine and low back pain is controversial. We examined the prevalence of abnormal findings on magnetic resonance imaging...
BACKGROUND
The relation between abnormalities in the lumbar spine and low back pain is controversial. We examined the prevalence of abnormal findings on magnetic resonance imaging (MRI) scans of the lumbar spine in people without back pain.
METHODS
We performed MRI examinations on 98 asymptomatic people. The scans were read independently by two neuroradiologists who did not know the clinical status of the subjects. To reduce the possibility of bias in interpreting the studies, abnormal MRI scans from 27 people with back pain were mixed randomly with the scans from the asymptomatic people. We used the following standardized terms to classify the five intervertebral disks in the lumbosacral spine: normal, bulge (circumferential symmetric extension of the disk beyond the interspace), protrusion (focal or asymmetric extension of the disk beyond the interspace), and extrusion (more extreme extension of the disk beyond the interspace). Nonintervertebral disk abnormalities, such as facet arthropathy, were also documented.
RESULTS
Thirty-six percent of the 98 asymptomatic subjects had normal disks at all levels. With the results of the two readings averaged, 52 percent of the subjects had a bulge at at least one level, 27 percent had a protrusion, and 1 percent had an extrusion. Thirty-eight percent had an abnormality of more than one intervertebral disk. The prevalence of bulges, but not of protrusions, increased with age. The most common nonintervertebral disk abnormalities were Schmorl's nodes (herniation of the disk into the vertebral-body end plate), found in 19 percent of the subjects; annular defects (disruption of the outer fibrous ring of the disk), in 14 percent; and facet arthropathy (degenerative disease of the posterior articular processes of the vertebrae), in 8 percent. The findings were similar in men and women.
CONCLUSIONS
On MRI examination of the lumbar spine, many people without back pain have disk bulges or protrusions but not extrusions. Given the high prevalence of these findings and of back pain, the discovery by MRI of bulges or protrusions in people with low back pain may frequently be coincidental.
Topics: Adult; Aged; Aged, 80 and over; Back Pain; Female; Humans; Intervertebral Disc; Intervertebral Disc Displacement; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Middle Aged; Prevalence; Sacrum
PubMed: 8208267
DOI: 10.1056/NEJM199407143310201 -
European Spine Journal : Official... Dec 2008Recent basic science studies on discogenic low back pain have provided new knowledge about this condition. This paper reviews some of these results and presents an... (Review)
Review
Recent basic science studies on discogenic low back pain have provided new knowledge about this condition. This paper reviews some of these results and presents an overview of the following findings. The rat lumbar intervertebral disk may be innervated non-segmentally through the paravertebral sympathetic nerve and segmentally through the sinuvertebral nerves, and also by dichotomizing sensory fibers. The exposure of the nucleus pulposus (NP) to the outer annulus fibrosus (AF) may induce nerve injury and ingrowth into the disk. Nerve growth factor (NGF)-sensitive neurons are predominant in the rat intervertebral disk, which indicates that hyperalgesic responses can be induced by inflammation. NGF in the NP may promote axonal growth. Lumbar fusion may inhibit nerve ingrowth into the degenerated disk and reduce the percentage of calcitonin gene related peptide (CGRP)-positive neurons.
Topics: Animals; Back Pain; Calcitonin Gene-Related Peptide; Fibrocartilage; Humans; Inflammation; Intervertebral Disc; Intervertebral Disc Displacement; Nerve Growth Factor; Nociceptors; Rats; Sensory Receptor Cells; Sympathetic Fibers, Postganglionic
PubMed: 19005695
DOI: 10.1007/s00586-008-0752-4 -
Postgraduate Medical Journal Feb 1951
Topics: Humans; Intervertebral Disc; Intervertebral Disc Displacement; Sciatica
PubMed: 14807871
DOI: 10.1136/pgmj.27.304.50 -
The Israel Medical Association Journal... Jan 2003
Topics: Contraindications; Humans; Intervertebral Disc; Postoperative Complications; Prosthesis Design; Prosthesis Implantation; Spinal Diseases; Spinal Fusion; Treatment Outcome
PubMed: 12592962
DOI: No ID Found -
International Journal of Molecular... Jan 2023The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and... (Review)
Review
The intervertebral disk degeneration (IDD) and its associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. IDD progresses with age, leading to spondylosis, spondylarthrosis, intervertebral disk herniation, and spinal stenosis. The purpose of this review is an attempt to summarize the data characterizing the patterns of production of pro-inflammatory and anti-inflammatory cytokines in IDD and to appreciate the prognostic value of cytokine imbalance as its biomarker. This narrative review demonstrates that the problem of evaluating the contribution of pro-inflammatory and anti-inflammatory cytokines to the maintenance or alteration of cytokine balance may be a new key to unlocking the mystery of IDD development and new therapeutic strategies for the treatment of IDD in the setting of acute and chronic inflammation. The presented data support the hypothesis that cytokine imbalance is one of the most important biomarkers of IDD.
Topics: Humans; Intervertebral Disc Degeneration; Cytokines; Intervertebral Disc Displacement; Biomarkers; Anti-Inflammatory Agents; Intervertebral Disc
PubMed: 36768679
DOI: 10.3390/ijms24032360 -
Journal of Biomedical Materials... Sep 2018Intervertebral disk (IVD) degeneration is a multifactor process that results in the physical destruction of the nucleus pulposus (NP) and annulus fibrosus (AF). This...
Intervertebral disk (IVD) degeneration is a multifactor process that results in the physical destruction of the nucleus pulposus (NP) and annulus fibrosus (AF). This compromises IVD function and causes significant disability and economic burden. Strategies to replace the entire composite structure of the IVD are limited and most approaches do not recapitulate the heterogenous biochemical composition, microarchitecture or mechanical properties of the native tissue. Our central hypothesis was that donor IVDs which resemble the size and biochemistry of human lumbar IVDs could be successfully decellularized while retaining the tissue's structure and function with the long-term goal of creating a composite scaffold for tissue engineering the human IVD. Accordingly, we optimized a procedure to decellularize bovine tail IVDs using a combination of detergents, ultrasonication, freeze-thaw cycles, and nucleases. The resultant decellularized whole IVD xenografts retained distinct AF and NP regions which contained no visible intact cell nuclei and minimal residual bovine deoxyribose nucleic acid (DNA; 65.98 ± 4.07 and 47.12 ± 13.22 ng/mg, respectively). Moreover, the NP region of decellularized IVDs contained 313.40 ± 50.67 µg/mg glycosaminoglycan. The presence of collagen type II was confirmed via immunohistochemistry. Additionally, histological analysis of the AF region of decellularized IVDs demonstrated retention of the native angle-ply collagen microarchitecture. Unconfined compression testing demonstrated no significant differences in swelling pressure and toe-region modulus between fresh and decellularized IVDs. However, linear region moduli, peak stress and equilibrium moduli were all significantly reduced. Together, this research demonstrates a successful initial step in developing a biomimetic acellular whole IVD xenograft scaffold for use in IVD tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2412-2423, 2018.
Topics: Animals; Annulus Fibrosus; Cattle; Cell Nucleus; Collagen; Compressive Strength; DNA; Extracellular Matrix; Glycosaminoglycans; Heterografts; Image Processing, Computer-Assisted; Intervertebral Disc; Nucleus Pulposus; Tissue Scaffolds
PubMed: 29673061
DOI: 10.1002/jbm.a.36434