A Comparison of Two Ovine Lumbar Intervertebral Disc Injury Models for the Evaluation and Development of Novel Regenerative Therapies

Global Spine J. 2018 Dec;8(8):847-859. doi: 10.1177/2192568218779988. Epub 2018 Jun 10.

Abstract

Study design: Large animal research.

Objective: Lumbar discectomy is the most commonly performed spinal surgical procedure. We investigated 2 large animal models of lumbar discectomy in order to study the regenerative capacity of mesenchymal stem cells following disc injury.

Methods: Twelve adult ewes underwent baseline 3-T magnetic resonance imaging (MRI) followed by lumbar intervertebral disc injury by either drill bit (n = 6) or annulotomy and partial nucleotomy (APN) (n = 6). Necropsies were performed 6 months later. Lumbar spines underwent 3-T and 9.4-T MRI prior to histological, morphological and biochemical analysis.

Results: Drill bit-injured (DBI) and APN-injured discs demonstrated increased Pfirrmann grades relative to uninjured controls (P < .005), with no difference between the 2 models. Disc height index loss was greater in the APN group compared with the DBI group (P < .005). Gross morphology injury scores were higher in APN than DBI discs (P < .05) and both were higher than controls (P < .005). Proteoglycan was reduced in the discs of both injury models relative to controls (P < .005), but lower in the APN group (P < .05). Total collagen of the APN group disc regions was higher than DBI and control discs (P < .05). Histology revealed more matrix degeneration, vascular infiltration, and granulation in the APN model.

Conclusion: Although both models produced disc degeneration, the APN model better replicated the pathobiology of human discs postdiscectomy. We therefore concluded that the APN model was a more appropriate model for the investigation of the regenerative capacity of mesenchymal stem cells administered postdiscectomy.

Keywords: animal model; discectomy; intervertebral disc; regeneration.