Ovine models of intervertebral disc degeneration

Abstract

The development and evaluation of effective therapeutic strategies for intervertebral disc degeneration (IVDD) and their successful incorporation into clinical practice remain challenging, largely due to the absence of an optimal preclinical animal model. While both induced and spontaneous IVDD animal models have provided valuable insights, they also present inherent limitations that restrict their translational applicability. Increasing evidence supports the use of sheep as a highly relevant large animal model, as spontaneous spine disorders in this species closely mirror many features of human IVDD. Sheep exhibit remarkable similarities to humans in terms of disc cellular composition, anatomical configuration, physiological loading, histological architecture, and molecular signaling pathways. These features make the ovine model uniquely positioned to bridge the gap between basic science and clinical translation, fulfilling both scientific and regulatory requirements. In this review, we highlight the shared features of IVDD between sheep and humans and examine both spontaneous and induced ovine models currently used to study disc degeneration. Furthermore, we discuss how the integration of advanced technologies, such as surgical navigation systems can refine the reproducibility and precision of these models. These innovations not only enhance experimental rigor but also strengthen the translational value of the ovine model, advancing our understanding of IVDD pathophysiology, diagnosis, prevention, and treatment. Continued refinement of ovine models will play a critical role in the development of effective therapeutic strategies for managing IVDD in humans.

Keywords: Spine; animal models; sheep.

Figure 1

Representative images illustrate comparative axial gross views of healthy lumbar intervertebral discs from human (left image), and ovine (right image) specimens, showcasing remarkable anatomical similarities. These visual comparisons accentuate shared structural features, enhancing our comprehension of the inter-species parallels in disc anatomy. The figure was reused from an open access article from Stolworthy et al. (19) under the terms of the Creative Commons Attribution 4.0 International License.

Figure 2

Representative images present comparative sagittal views of lumbar intervertebral discs from human (first row) and ovine (second row) specimens, showcasing notable anatomical similarities. Grades 1–5 have been assigned according to the Thompson grading scale for gross disc changes (40), and their translation to the ovine model. These visual comparisons emphasize shared structural features, enhancing our understanding of interspecies parallels in gross disc anatomy. The figure was reused from an open access article from Lee et al. (41) under the terms of the Creative Commons Attribution 4.0 International License.

Figure 3

Diagram illustrating the differences between healthy (“naïve”) ovine lumbar intervertebral discs (left) and those with physically induced degeneration (right). The top images depict the gross morphology of an intact disc compared to a disc 32 weeks post-partial annulotomy, showing evident structural deterioration. The bottom images present T2-weighted MRI scans of the same discs, where the healthy disc (left) exhibits high signal intensity in the nucleus pulposus, reflecting normal hydration, while the degenerated disc (right) shows a markedly reduced signal, consistent with loss of hydration and disc degeneration. MRI, magnetic resonance imaging.

Figure 4

Cross-sections of a human (left) and ovine (right) intervertebral disc, both exhibiting degenerative changes. The human disc shows a dehydrated, discolored nucleus pulposus (arrow) surrounded by intact annulus fibrosus rings. The ovine disc demonstrates similar spontaneous, age-related degeneration from a 9-year-old (1). Attempting to investigate these degenerative changes has led to the development of a large number of animal models. In most studies these animal models have been either small or large old sheep. This comparison underscores the morphological parallels in disc degeneration between the two species. Ovine disc is an original image from the authors. Human disc image modified and used with permission of Ruel et al. (51).

Figure 5

Application of intraoperative imaging and surgical navigation for spine surgery in an ovine model of intervertebral disc degeneration. (A) Intraoperative photograph demonstrating the use of an O-arm integrated with and Stealthstation S8 (Medtronic, USA) for real-time surgical navigation. The image shows the planned trajectory to access the T12 vertebra in a 6-month-old sheep using a minimally invasive approach. (B) Intraoperative CT image confirming accurate pedicle screw placement at T12 was achieved. CT, computed tomography.