Abstract
This issue is a compilation of articles focused on all aspects of spine research, ranging from noninvasive therapies to imaging to review of therapeutic options to basic science. The broad distribution of studies highlights the complexity of the spinal unit (including its intervertebral discs and vertebral bodies), our limited understanding of the etiology and pathogenesis of disc degeneration, and also, perhaps not surprisingly, its relation to back pain or the best way to treat these disorders. These articles attempt to address these topics.
A review by Eisenstein et al. briefly describes the mechanical functioning and anatomy within the spine, followed by a summary of the main interventional surgeries currently available. However, the world of regenerative medicine may be about to change this field altogether, with the culmination of one of the largest cell therapy trials due out this year, treating chronic back pain patients with allogeneic cells.
Noninvasive therapies for back pain have been shown to be effective in a large number of individuals with acute symptoms. Steele et al. show that at 12-week follow-up isolated lumbar extension resistance training improves strength and back pain in individuals with chronic low back pain. Longer term follow-up will be required to confirm the efficacy of this treatment but this study suggests it is a potential therapy for pain.
Pachowsky et al. used quantitative T2 mapping by 3-T magnetic resonance imaging to demonstrate development of degeneration in adjacent intervertebral discs following vertebral augmentation or kyphoplasty for vertebral body fractures. This analysis was done on average 28 months posttreatment and the adjacent discs were compared with those that were nonadjacent to the treated vertebral body.
Spinal fusion is a commonly used treatment for symptomatic disc degeneration. Unfortunately, about 30% of these interventions fail for a variety of reasons. Identification of ways to enhance the success of this approach would have a significant impact. Owen et al. demonstrate that nucleus pulposus cells have the potential to mineralize. This observation is important as it suggests that cell injections, instead of being used for biological repair of the disc, could be utilized instead to improve the success of fusion. This is a very novel idea.
Hondke et al. show that annulus fibrosus cells retain their potential for proliferation, migration, and extracellular matrix accumulation independent of the degeneration status of the tissue they are isolated from. This shows that these cells may be suitable to use for biological repair even when sourced from very degenerate discs. Annulus fibrosus damage is one cause of disc degeneration and is a common cause of reherniation following discectomy. Zhou et al. show the effectiveness of the chemokine CCL5 to induce annulus cell migration. This raises the possibility of an alternative way to stimulate endogenous repair. Unfortunately, implantation of CCL5-laden fibrin gels in sheep discs did not result in annulus cell homing to the defect, highlighting the importance of testing new therapeutic approaches in animal models. Interestingly, Farrugia et al. show that endogenous repair of annular defects can occur in sheep. They use glycosaminoglycan sulfation motif epitope immunostaining to show that this repair has features similar to development.
The nucleus pulposus is composed of both notochordal cells and nucleus pulposus cells (to varying extents between species). Saggese et al. showed these 2 cell types respond differently to hydrostatic pressure and glucose restriction. These functional differences could explain why animal species that retain notochord cells are less likely to develop disc degeneration. It was interesting to note that for the parameters assessed nucleus pulposus cells were unaffected by low (0.5 mM) glucose levels, typical of those often found in the intervertebral disc. This is an important finding as it may also explain why these cells can survive in vivo in a low-glucose environment.
Clinical translation of experimental regenerative medicine approaches to repair the degenerate disc is limited, in part, by our ability to identify appropriate cell sources suitable for this purpose. Identification of biomarkers of the specific cell types present in the disc is critical to overcome this. Van den Akker et al. use whole transcriptome analysis to identify novel surface cell markers of human nucleus pulposus and annulus fibrosus cells obtained from scoliotic, healthy, and degenerate discs. They compare the findings to immortalized cell lines.
Finally, a very interesting in vivo study by Duarte et al. has been undertaken investigating the etiology of degeneration and pain in neurosegmentally linked cartilages via neurogenic inflammation. They report that when joint degeneration resembling osteoarthritis is induced in the L5-6 spinal facet joints, there is not only an increase in substance P at this location contributing to the pathogenesis but also increased levels and degeneration in knee articular cartilage (if neurosegmentally linked) of the same animals. This indicates even further complexities with maintaining the homeostasis of these spinal tissues.
We hope you enjoy reading these articles.