MRI provides proof of regenerated human intervertebral discs in the spine
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The retrieved literature includes case reports, animal studies, and small preliminary surgical cohorts suggesting that MRI can monitor indicators of disc recovery or regeneration (such as increased signal intensity or height). However, these studies provide only partial evidence or preclinical proof of concept rather than definitive clinical proof of regenerated human intervertebral discs.
Objective: The aim of this study was to evaluate disc metabolism after decreasing the axial load through surgery by assessing the glycosaminoglycan content through a non-invasive method—delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). Methods: Sixteen patients with mono-segmental disc degeneration (L4-L5 or L5-S1) who underwent posterior lumbar spine fixation with intervertebral distraction of 2 consecutive vertebrae using monoaxial transpedicular screws and lyophilized allograft to achieve segmental fusion, and who had a follow-up period of at least 2 years, were included in this study. The first lumbar disc was used as the control group. The dGEMRIC studies in degenerative and control discs, visual analogue scale (VAS), Oswestry disability index (ODI), lumbar lordosis, and disc thickness were reviewed before and after surgery. Results: Visual analogue scale and ODI showed significant improvements (P = .003, P = .0004, respectively). The thickness of the operated discs was increased by an average of 2.41 mm (P = .0004) while maintaining lumbar lordosis (P = .35). In pre- and post-surgery dGEMRIC studies, the operated discs showed a significant difference (P = .0013), while the control groups remained approximately unchanged (P = .87). Conclusion: We have demonstrated that by restoring the disc height and reducing the associated pressure, the glycosaminoglycan content can be increased in the discs, as indicated by a decrease in gadolinium binding. Our results suggest that eliminating pressure on intervertebral discs can prevent their degeneration and initiate the regeneration process. Level of Evidence: Level IV, Therapeutic study.
pmc Acta Orthop Traumatol Turc Acta Orthop Traumatol Turc 3544 aott Acta Orthopaedica et Traumatologica Turcica 1017-995X 2589-1294 Turkish Association of Orthopaedics and Traumatology PMC11740234 PMC11740234.1 11740234 11740234 39876574 10.5152/j.aott.2024.24034 aott-58-6-346 1 Research Article Intervertebral disc regeneration – Is it possible? Schiopu Dragos 1 http://orcid.org/0009-0001-6517-7232 Devriendt Arnaud 2 Van Vyve Clara 3 http://orcid.org/0000-0002-7578-3877 Illes Tamas S.
Methods: Sixteen patients with mono-segmental disc degeneration (L4-L5 or L5-S1) who underwent posterior lumbar spine fixation with intervertebral distraction of 2 consecutive vertebrae using monoaxial transpedicular screws and lyophilized allograft to achieve segmental fusion, and who had a follow-up period of at least 2 years, were included in this study. The first lumbar disc was used as the control group. The dGEMRIC studies in degenerative and control discs, visual analogue scale (VAS), Oswestry disability index (ODI), lumbar lordosis, and disc thickness were reviewed before and after surgery.
Our results suggest that eliminating pressure on intervertebral discs can prevent their degeneration and initiate the regeneration process. Level of Evidence: Level IV, Therapeutic study. Keywords Lumbar disc Regeneration Posterior distraction dGEMRIC The authors declared that this study has received no financial support.
pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY-NC Highlights Functioning of the intervertebral disc (IVD) strongly depends on the glycosaminoglycan (GAG)
7 During postoperative MRI, artifacts caused by implanted metals can make the assessment difficult in the image plane (in-plane artifacts) and adjacent planes (through-plane artifacts). We dispose by many methods to reduce in an important way the artifacts’ phenomenon caused by the presence of metal material after spine surgery. The simple modification of the MRI scanning protocol and the use of titanium rods and screws for implantation may produce good images with fewer artifacts.
Discussion Most lumbar spine specialists agree that lumbar instability is based on IVD degeneration and is considered one of the major factors triggering low back pain. After the lack of success of conservative treatment, spinal arthrodesis surgery by posterior transpedicular fixation supplemented by ventral fusion of the vertebral bodies is the operation of choice. Ventral fusion (PLIF, TLIF, ALIF, etc.) invariably involves the intervertebral disc’s sacrifice and significantly reduces lumbar spine movements. 16 The lumbar 360° fusion eliminates instability and usually improves pain and neurological symptoms.
In the same study, magnetic resonance imaging showed a change in the MRI signal in T2-weighting. 21 , 22 Among the limitations of our study, we can mention the small number of cases, the lack of a non-invasive analysis of the state of the intervertebral disc (for example, dGEMRIC) after at least 2 years, and the still small follow-up period. However, following the positive results of this preliminary study, we have initiated a prospective randomized clinical study on a more significant number of patients with single or more operated levels. The long-term goal is to perform temporal distraction on IVDs until final disc regeneration can be established.
This would eliminate the need to sacrifice IVD in spinal fusion surgeries. Temporal distraction supplemented with molecular therapy could provide an opportunity to preserve spinal physiology. Figure 1. Preoperative lumbar spine sagittal and coronal x-rays show a grade I spondylolisthesis between the L4 and L5 vertebrae as a sign of instability. Figure 2. Postoperative lumbar spine sagittal and coronal x-rays at 6 months show L4-L5 transpedicular fixation. The height of the intervertebral disc L4-L5 increased and the spondylolisthesis disappeared. No inter-somatic fusion was observed. Figure 3.
Serial changes observed by magnetic resonance imaging in the intervertebral disc after chemonucleolysis. A consideration of the mechanism of chemonucleolysis.
Changes in the intervertebral disc after chemonucleolysis in 26 patients were observed by magnetic resonance imaging for 1 year, and from the results a mechanism for chemonucleolysis was considered. A reduction in size of the herniation was not recognized 2 weeks after treatment, when chymopapain had caused necrosis of the disc, but began after 4 weeks, when regeneration of the disc had occurred. The herniation was further reduced after 3 months, and the disc had become fibrocartilaginous in a cicatricial process. Marked decrease in disc signal was observed after 2 weeks, and never recovered. From these facts, it is considered that chymopapain might never cause primary diminution of disc herniation, and any reduction of herniation that occurs is due to the effects of a secondary cicatricial contraction.
Published in Spine (1992)
Chymopapain, chemonucleolysis, and nucleus pulposus regeneration. A biochemical and biomechanical study. In the adult mongrel dog, in vivo injection of chymopapain into the intervertebral disc resulted, at two weeks, in disc space narrowing. However, [35S]sulfate labeling and proteoglycan characterization demonstrate that the nucleus retains the ability to synthesize proteoglycans, although they were degraded rapidly by residual proteolytic activity. Three months following chymopapain treatment, the intervertebral dog disc shows that an increase in disc height, return of nuclear material, and proteoglycan aggregate is present. At six months following chymopapain treatment, proteoglycans of similar characteristics to normal canine intervertebral disc are identified with a glucosamine/galactosamine ratio approaching normal values. Biomechanically, the short-term (30-120 minutes) in vitro effects of chymopapain appear to be the same as the carrier causing increased disc height, stiffness values, and creep rates.
Glucosamine and chondroitin sulfate preparations are widely used as food supplements against osteoarthritis, but critics are skeptical about their efficacy, because of the lack of convincing clinical trials and a reasonable scientific rationale for the use of these nutraceuticals. Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals. Oral intake of glucosamine and chondroitin sulfate for two years associated with disk recovery (brightening of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a biochemical explanation for the possible efficacy of these nutraceuticals. They are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and inhibit the breakdown of their extracellular matrix proteoglycans. The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage. However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general.
Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals.
Case presentation Oral intake of glucosamine and chondroitin sulfate for two years associated with disk recovery (brightening of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a biochemical explanation for the possible efficacy of these nutraceuticals. They are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and inhibit the breakdown of their extracellular matrix proteoglycans. Conclusion The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage.
However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general. status released display-pdf yes is-olf no is-manuscript no is-preprint no is-journal-matter no is-scanned no is-retracted no Received 2003 Feb 10; Accepted 2003 Jun 10; Collection date 2003.
In addition, we discuss the biochemistry of cartilage degeneration and of possible regeneration by these supplements. Matrix repair is feasible at early stages of degradation [ 19 ] and involves restoration of glycosaminoglycan structure and associated water content (to be discussed below). This is most easily monitored by magnetic resonance imaging, particularly T2-weighted MRI [ 20 ]. Sequential MRI-imaging studies have recently likewise been employed successfully in longitudinal studies of lumbar disc degeneration [ 21 ] and to monitor healing of fractured and herniated intervertebral discs [ 22 , 23 ].
Disc L4-5 showed signs of an advanced state of degeneration, and no improvement but also no worsening of this disc (endplates morphologically unchanged) over the 2 years period. Figure 1 Disc cartilage regeneration during 2 years of supplement intake . T2-weighted MR images of lumbar spine, made in September 1999 (start of supplement intake), 2000 and 2001. Note the increase of MRI signal of disc L3-4 (thick arrows) and disappearance of focal disc protrusion (thin arrow) of this disc. Note that the fully degenerated L4-5 disc remains unchanged. Upper panels and lower panels represent two consecutive images of planes 4 mm apart.
Discussion of MRI finding This case report illustrates the value of MRI to monitor disc quality improvement in the lumbar spine. After oral intake of glucosamine and CS for two years, an increased water retention (and less bulging/protrusion) in the partially degenerated L3-4 disc was seen, but not in the almost fully degenerated L4-5 disc, where probably little or no functional chondrocytes are left. These findings agree with a clinical study where radiographically mild forms of knee osteoarthritis showed significant improvement by supplement intake, while severe osteoarthritis did not [ 24 ].
The present case showed, for the first time, normalizing MRI signals of a degenerated disc in the lumbar spine, suggesting (but not proving) that, indeed, this food supplement may have gradually led to anatomic improvement of the disc. Since discs are avascular and the compounds have to reach the chondrocytes via intermittent pressure-dependent diffusion, we surmise, in agreement with a recent study [ 21 ], that it may have been important that the patient maintained spine mobility by sport activities to facilitate disc regeneration.
Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc (IVD). This study investigates the ability of an injectable hydrogel (NPgel), to inhibit catabolic protein expression and promote matrix expression in human nucleus pulposus (NP) cells within a tissue explant culture model isolated from degenerate discs. Furthermore, the injection capacity of NPgel into naturally degenerate whole human discs, effects on mechanical function, and resistance to extrusion during loading were investigated. Finally, the induction of potential regenerative effects in a physiologically loaded human organ culture system was investigated following injection of NPgel with or without bone marrow progenitor cells. Injection of NPgel into naturally degenerate human IVDs increased disc height and Young's modulus, and was retained during extrusion testing. Injection into cadaveric discs followed by culture under physiological loading increased MRI signal intensity, restored natural biomechanical properties and showed evidence of increased anabolism and decreased catabolism with tissue integration observed. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. STATEMENT OF SIGNIFICANCE: Low back pain resulting from disc degeneration is a leading cause of disability worldwide. However, to date few therapies target the cause and fail to repair the intervertebral disc. This study investigated the potential regenerative properties of an injectable hydrogel system (NPgel) within human tissue samples. To mimic the human in vivo conditions and the unique IVD niche, a dynamically loaded intact human disc culture system was utilised. NPgel improved the biomechanical properties, increased MRI intensity and decreased degree of degeneration. Furthermore, NPgel induced matrix production and decreased catabolic factors by the native cells of the disc. This manuscript provides evidence for the potential use of NPgel as a regenerative biomaterial for intervertebral disc degeneration.
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