A porcine model of intervertebral disc degeneration induced by annular injury characterized with magnetic resonance imaging and histopathological findings. Laboratory investigation. J Neurosurg Spine

Department of Neurosurgery, Inha University Hospital, Incheon, Korea.
Journal of Neurosurgery Spine (Impact Factor: 2.38). 06/2008; 8(5):450-7. DOI: 10.3171/SPI/2008/8/5/450
Source: PubMed


Appropriate animal models of disc degeneration are critical for the study of proposed interventions as well as to further delineate the degenerative process. The purpose of this study was to characterize a porcine model for disc degeneration confirmed on magnetic resonance (MR) imaging studies and histological analysis.
Twelve miniature pigs were used (weight 48-65 kg) to study degeneration in the lumbar spine. Under fluoroscopic guidance, the disc was percutaneously punctured with a 3.2-mm-diameter trephine to a 5-mm depth into the annulus fibrosus. Control and experimental levels were randomized among 6 levels in the lumbar spine. The unlesioned spinal levels were used as controls and were compared with lesioned levels. Magnetic resonance imaging grading and disc height were serially recorded preoperatively, and at 5, 8, 19, 32, and 39 weeks postoperatively. The animals were killed in groups of 3 at 7, 18, 32, and 41 weeks postinjury, and the discs were examined histopathologically.
Consistent, sequential, and progressive degeneration of the annular injury was observed on MR imaging and histopathological studies from the time of injury to the final time point. The disc height and the disc height index also sequentially decreased from the time of the injury in a consistent manner. The uninjured control levels did not show any progressive degeneration and maintained their normal state.
Based on MR imaging and histopathological findings, the authors demonstrated and characterized a reliable model of sequential disc degeneration in miniature pigs with percutaneous injury to the annulus fibrosus. In the early stages, as soon as 5 weeks after injury, significant disc degeneration was seen on MR imaging grading with decreases in disc height. This degeneration did not improve by the final time point of 39 weeks.

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    • "BMP13 treatment resulted in prevention of cell loss (or cell mobilisation), prevention of neo-vascularisation, deposition of collagen fibres in the AF, production of proteoglycans in the NP, and retention of the original disc height. A model of annular injury was also described in miniature pigs, where consistent sequential and progressive degeneration was observed that did not improve by the final time point of 39 weeks (Yoon et al., 2008). Furthermore, a porcine annular puncture model was utilised to test the efficacy of non-cell-based materials to prevent the recurrence of disc herniation (Wang et al., 2007). "
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    ABSTRACT: Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review.
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    • "Indeed, the discs of both large and small animals possess anatomical and biomechanical traits that make them suitable models for studying the human condition (O’Connell et al., 2007b; Beckstein et al., 2008). Techniques for initiating degenerative changes in such model systems include AF injury (Elliott et al., 2008; Yoon et al., 2008), mechanical overload (Iatridis et al., 1999; Kroeber et al., 2002) and enzymatic treatment to reduce NP glycosaminoglycan content (Boxberger et al., 2008; Hoogendoorn et al., 2007). There are also a few animals that develop disc degeneration spontaneously, such as the sand rat and chondrodystrophoid dog (Gruber et al., 2002; Hansen, 1952). "
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    ABSTRACT: Degeneration of the intervertebral discs, a process characterized by a cascade of cellular, biochemical, structural and functional changes, is strongly implicated as a cause of low back pain. Current treatment strategies for disc degeneration typically address the symptoms of low back pain without treating the underlying cause or restoring mechanical function. A more in-depth understanding of disc degeneration, as well as opportunities for therapeutic intervention, can be obtained by considering aspects of intervertebral disc development. Development of the intervertebral disc involves the coalescence of several different cell types through highly orchestrated and complex molecular interactions. The resulting structures must function synergistically in an environment that is subjected to continuous mechanical perturbation throughout the life of an individual. Early postnatal changes, including altered cellularity, vascular regression and altered extracellular matrix composition, might set the disc on a slow course towards symptomatic degeneration. In this Perspective, we review the pathogenesis and treatment of intervertebral disc degeneration in the context of disc development. Within this scope, we examine how model systems have advanced our understanding of embryonic morphogenesis and associated molecular signaling pathways, in addition to the postnatal changes to the cellular, nutritional and mechanical microenvironment. We also discuss the current status of biological therapeutic strategies that promote disc regeneration and repair, and how lessons from development might provide clues for their refinement.
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