Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies

Abstract

Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used. By the transpedicular approach, a 2 mm tunnel was drilled to the NP through the EP. A partial-nucleotomy was performed. The tunnel was sealed using a polyurethane scaffold. Lumbar discs were assigned to different groups: L1-2: nucleotomy; L2-3: EP tunnel; L3-4: nucleotomy + EP repair; L4-5: EP tunnel + repair; L5-6: control. X-Ray and MRI were performed at 0, 1, 3, and 6 months after surgery. Disc height and MRI indexes were calculated. Macro- and micro-morphology were analyzed. Pfirrmann and Thompson grades were assigned. The treated discs exhibited a progressive decrease in NP signal intensity and MRI index, displaying specific grades of degeneration based on the surgical treatment. According to Pfirrmann and Thompson grades different procedures were staged as: EP tunnel + repair: grade-II; EP tunnel: grade-III, nucleotomy + EP repair: grade-IV; nucleotomy: grade-V. A new stepwise model of IDD to study and test safety and efficacy of novel strategies for NP regeneration has been characterized. The different degrees of IDD have been observed similar to Pfirrmann and Thompson grading system. The intact AF allows for loading studies and eliminating the need for AF closure. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2460-2468, 2018.

Effect of Fatigue Load on Internal Mechanical Properties of the Intervertebral Disc

“…The intervertebral disc is constructed of a central gel-like nucleus pulposus surrounded by a peripheral firm annulus fibrosus, these tissues play different roles in the biomechanical function of the intervertebral disc (Flouzat-Lachaniette et al, 2018). Outer AF can resist tensile load and surround inner AF, while the nucleus pulposus can provide a hydrostatic barrier to limit the deformation (Vadalà et al, 2018). Some scholars have proposed the hypothesis for the fatigue mechanism of the intervertebral disc, based on the specific property of the hydraulic effect of the nucleus pulposus.…”

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

“…Major contributors include aging [38], smoking [52], mechanical overload [53], obesity [54], and diabetes [55]. The structural hallmark of IDD is the progressive dehydration of the NP mainly due to the gradual loss of proteoglycans within the ECM [19,56]. The principal proteolytic enzymes involved include the matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) [57] which are upregulated together with proinflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-(IL-) 6, IL-1, IL-17, and interferon γ (IFN-γ) [51], while anabolic factors, such as IGF-1 [58] and TGF-β [59], appear to be downregulated.…”

The research of transgenic human nucleus pulposus cell transplantation in the treatment of lumbar disc degeneration

“…Researchers at home and abroad have come up with cell transplantation to delay or cure lumbar disc degeneration, based on molecular biology fundamental researches on lumbar disc degeneration . In addition, the use of tissues engineering to treat lumbar disc degeneration has become a new direction in the field of spine research, making it possible to cure lumbar disc degeneration at the root …”