Abstract
The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs.
Highlights
The intervertebral disc (IVD) is a tough but intricately organized connective tissue which resists tension and weight bearing during axial and torsional spinal loading and provides spinal stability and flexibility [1]
The hydration provided by the hydrophilic proteoglycans of the nucleus pulposus (NP) afford viscoelastic and hydrodynamic properties which equip the IVD with its ability to act as a weight bearing cushion [5]
Type II collagen is present in the annulus fibrosus (AF) but to a far lesser extent, the NP is rich in type II collagen where type II fibrillar networks entrap the hyaluronan (HA)-aggrecan-link ternary complexes which are so important for discal biomechanical function [8,9,10,11]
Summary
The intervertebral disc (IVD) is a tough but intricately organized connective tissue which resists tension and weight bearing during axial and torsional spinal loading and provides spinal stability and flexibility [1]. Superior and inferior endplates of hyaline cartilage, the cartilaginous endplates (CEPs), enclose the NP where it borders the spinal vertebrae. This arrangement of connective tissues equips the IVD with unique weight-bearing capability [4]. Type II collagen is present in the AF but to a far lesser extent, the NP is rich in type II collagen where type II fibrillar networks entrap the hyaluronan (HA)-aggrecan-link ternary complexes which are so important for discal biomechanical function [8,9,10,11]. The loss of aggrecan from the IVD lessens its ability to swell and act as a weight-bearing cushion and traumatic mechanical damage to the NP may be irreversible, distinguishing degenerative disc disease (DDD) from normal aging of the IVD [22]. Loss of discal aggrecan promotes angiogenesis, and may lead to the ingrowth of blood vessels and nociceptive nerves and perception of discogenic low back pain (LBP) [23,24]
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