Intervertebral disc disease in dogs – Part 1: A new histological grading scheme for classification of intervertebral disc degeneration in dogs

Bergknut, Niklas; Meij, Björn P.; Hagman, Ragnvi; Nies, K.S. de; Rutges, J.P.H.J.; Smolders, Lucas A.; Creemers, Laura B.; Lagerstedt, Anne-Sofie; Hazewinkel, H.A.W.; Grinwis, Guy C. M.

doi:10.1016/j.tvjl.2012.05.027

Cited by 59 publications

(117 citation statements)

References 25 publications

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“…3 Each half of the disc was scored separately incorporating all disc elements (AF and NP), cartilaginous endplates, and adjacent vertebral bodies. However, the scoring of notochordal cell presence was eliminated because of the absence of these cells in chondrodystrophoid phenotype sheep discs.…”

Section: Histological Analysismentioning

confidence: 99%

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Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

SPI

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OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

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Section: Histological Analysismentioning

confidence: 99%

“…6). First, none of the treatment groups had scores that fell within the low degeneration score range (1)(2)(3)(4)(5)(6). Moreover, the highest degeneration scores (13)(14)(15)(16)(17)(18)(19) were Fig.…”

Section: Histological Analysismentioning

confidence: 99%

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

SPI

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“…6 Each half of the disc was scored separately (for example, AF1 and AF2), incorporating all disc elements (AF and NP), cartilaginous endplates (CEPs), and adjacent vertebral bodies (VBs). In addition, the scoring of notochordal cell presence was eliminated due to the chondrodystrophoid phenotype of the sheep disc.…”

Section: Histological Analysismentioning

confidence: 99%

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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Object Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration. Methods A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically. Results No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs. Conclusions These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.

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“…However, recent studies have shown that degeneration of IVDs in NCD breeds involves replacement of the notochordal cells with chondrocyte-like cells, i.e. that the changes are similar to those taking place in the CD breeds (Bergknut et al, 2013a, Bergknut et al, 2012b, Kranenburg et al, 2013. This conflicts with Hansen's thesis of a fibrous type of metaplasia.…”

Section: Introductionmentioning

confidence: 85%

“…To evaluate the histological changes during IVD degeneration, Boos et al (2002) have developed a histological grading scheme for midsagittal sections of human lumbar IVDs. This grading scheme has been modified and validated for use in dogs of both breed types by Bergknut et al (2013a) and was used in this thesis for assessment of the histological changes.…”

Section: Introductionmentioning

confidence: 99%

The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs

et al. 2017

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The myth of fibroid degeneration in the canine intervertebral disc -A histopathological comparison of disc degeneration in chondrodystrophic and nonchondrodystrophic dogs Myten om fibroid degeneration i hundens intervertebraldiskerEn histopatologisk jämförelse av diskdegeneration mellan chondrodystrofa och icke chondrodystrofa hundar Tove Hansen Supervisor: Niklas Bergknut, Department of Clinical Sciences Examiner: Ragnvi Hagman, Department of Clinical Sciences Degree Project in Veterinary Medicine SUMMARYIn the 1950's, the veterinary pathologist, Hans-Jörgen Hansen noticed several dissimilarities between so called chondrodystrophic and non-chondrodystrophic dog breeds regarding intervertebral disc degeneration and related diseases. Chondrodystrophic breeds are characterized by disproportionally short extremities due to disturbances in the endochondral ossification whereas non-chondrodystrophic breeds have normal bodily constitutions. The two breed types often differ regarding age of onset of disease, spinal location and severity of clinical signs. He also noted different histopathological patterns during the course of degeneration, foremost in the centre of the intervertebral disc, the nucleus pulposus. Due to this, he named the degenerative processes chondroid metamorphosis and fibroid metamorphosis in chondrodystrophic and non-chondrodystrophic breeds respectively. In general, chondroid metamorphosis refers to the replacement of the original cell type (the notochordal cell) with chondrocyte-like cells, whereas the fibroid metamorphosis refers to replacement of these cells with fibrocyte-like cells. This distinction has since then been an accepted distinction between the two breed types. However, more recent studies indicate that the histopathological patterns are more similar in the two breed types than previously described, and that the chondroid metamorphosis might be the degenerative process taking place in both breed types.In this study the histopathological appearances of 42 intervertebral discs from 16 chondrodystrophic and 17 non-chondrodystrophic dogs in early stage intervertebral disc degeneration were examined. After midsagittal transection of the spines, the intervertebral discs were graded macroscopically between one and three on a five-grade scale (the Thompson grading scheme). Subsequently, each intervertebral disc was individually fixated in formalin and decalcified in EDTA. After decalcification, the intervertebral discs were embedded in paraffin, sliced with a microtome and stained with Hematoxilin and Eosin and Alcian Blue/Picrosirius Red. The histological samples were thereafter graded according to a histological grading scheme (the Boos grading scheme) after which the histological scores were compared between chondrodystrophic and non-chondrodystrophic dogs.The results showed that there was a significant difference in total histological scores between chondrodystrophic and non-chondrodystrophic dogs in the two lowest macroscopical grades of degeneration. Chondrodystrophic dogs had a highe...

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Intervertebral disc disease in dogs – Part 1: A new histological grading scheme for classification of intervertebral disc degeneration in dogs

Cited by 59 publications

References 25 publications

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs

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