The transpedicular surgical approach for the development of intervertebral disc targeting regenerative strategies in an ovine model

Fournier, L; Fusellier, Marion; Halgand, Boris; Lesoeur, Julie; Gauthier, Olivier; Meneï, Philippe; Montero‐Menei, Claudia N.; Guicheux, Jérôme; Clouet, Johann

doi:10.1007/s00586-017-5199-z

Cited by 13 publications

(19 citation statements)

References 38 publications

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“…Moreover, our study shows that sealing the small endplate tunnel with the PU scaffold prevent the formation of Shmorl Nodes and the progression of the degeneration grade. A further limitation is that this approach is surgical challenged as it has been reported . Therefore, few issues, such spinal canal invasion and bonny fragment extrusion in the disc space, need to be solved with new technologies .…”

Section: Discussionmentioning

confidence: 99%

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

Vadalà

Russo

Strobel

et al. 2018

Journal Orthopaedic Research

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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.

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Section: Discussionmentioning

confidence: 99%

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

Vadalà

Russo

Strobel

et al. 2018

Journal Orthopaedic Research

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“…The sheep received a bolus hypocoagulant dose of heparin (50 IU/kg) and were euthanized with an overdose of barbiturates (60 mg/kg) in accordance with the current best practices and legislation (European Directive 2010/63/EU). Post-euthanasia medullar MRI of the thoracolumbar sheep spines were performed to obtain T2-weighted images (TE: 86 ms, TR: 3,000 ms; slice thickness: 3 mm), using a 1.5 T MRI scanner (Magnetom Essenza®, Siemens Medical Solutions, Erlangen, Germany) [59]. Post-euthanasia X-ray imaging was conducted using a radiography machine (Convix 80® generator and Universix 120 table) from Picker International (Uniontown, Ohio, USA), to obtain coronal and sagittal plane radiographs of the sheep lumbar spines, with a collimator-to-film distance of 100 cm, an exposure of 100 mAs, and a penetration power of 48 kVp.…”

Section: Ovine Ivd Isolationmentioning

confidence: 99%

Controlled release of biological factors for endogenous progenitor cell migration and intervertebral disc extracellular matrix remodelling

et al. 2020

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The recent description of resident stem/progenitor cells in degenerated intervertebral discs (IVDs) supports the notion that their regenerative capacities could be harnessed to stimulate endogenous repair of the nucleus pulposus (NP). In this study, we developed a delivery system based on pullulan microbeads (PMBs) for sequential release of the chemokine CCL-5 to recruit these disc stem/progenitor cells to the NP tissue, followed by the release of the growth factors TGF-β1 and GDF-5 to induce the synthesis of a collagen type II-and aggrecan-rich extracellular matrix (ECM). Bioactivity of released CCL5 on human adipose-derived stem cells (hASCs), selected to mimic disc stem/progenitors, was demonstrated using a Transwell® chemotaxis assay. The regenerative effects of loaded PMBs were investigated in ex vivo spontaneously degenerated ovine IVDs. Fluorescent hASCs were seeded on the top cartilaginous endplates (CEPs); the degenerated NPs were injected with PMBs loaded with CCL5, TGF-β1, and GDF-5; and the IVDs were then cultured for 3, 7, and 28 days to allow for cell migration and disc regeneration. The PMBs exhibited sustained release of biological factors for 21 days. Ex vivo migration of seeded hASCs from the CEP toward the NP was demonstrated, with the cells migrating a significantly greater distance when loaded PMBs were injected (5.8 ± 1.3 mm vs. 3.5 ± 1.8 mm with no injection of PMBs). In ovine IVDs, the overall NP cellularity, the collagen type II and the aggrecan staining intensities, and the Tie2+ progenitor cell density in the NP were increased at day 28 compared to the control groups. Considered together, PMBs loaded with CCL5/TGF-β1/GDF-5 constitute an innovative and promising strategy for controlled release of growth factors to promote cell recruitment and extracellular matrix remodelling.

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“…This is inspired by methods used classically in spinal surgery for osteosynthesis (Ringel et al, 2006) and cementoplasty (Galibert et al, 1987;Taylor et al, 2007) and has to be performed by well-trained surgeons. The size of the surgical approach rules out its use on the smallest animal species, reserving it for the largest, such as sheep and pigs (Le Fournier et al, 2017;Vadalà et al, 2018). This technique can also be used to explore IVD degeneration or as a route to inject treatments into the NP.…”

Section: Structural Modelsmentioning

confidence: 99%

Degenerative lumbar disc disease: in vivo data support the rationale for the selection of appropriate animal models

Fusellier¹,

Clouet²,

Gauthier³

et al. 2020

eCM

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Since low-back pain is increasing in ageing populations, current research efforts are focused on obtaining a better understanding of the pathophysiology of intervertebral disc degeneration and on developing new therapeutic strategies. This requires adequate and clinically relevant models of the disease process. Ex vivo models can provide insights into isolated aspects of the degenerative/regenerative processes involved; although, ultimately, in vivo models are needed for preclinical translational studies. Such models have been developed in numerous animal species with significant variations in size and disc physiology and their number is considerable. Importantly, the choice of the model has to be tailored to the aim of the study. Given the number of available options, it is important to have a good understanding of the various models of disc degeneration and to be fully aware of their advantages and limitations. After comparing the anatomy and histology of intervertebral discs in animals and humans, the present study provides an overview of the different models of in vivo disc degeneration. It also provides a comprehensive guide with suggested criteria to select the most appropriate animal model in a question-driven manner.

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The transpedicular surgical approach for the development of intervertebral disc targeting regenerative strategies in an ovine model

Abstract: TPA induces damage to the endplates, and it may lead to neurological impairment and leakage of injected materials into the systemic circulation. These adverse effects must be fully considered before proceeding with TPA for IVD regenerative strategies.

Cited by 13 publications

References 38 publications

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

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

Controlled release of biological factors for endogenous progenitor cell migration and intervertebral disc extracellular matrix remodelling

Degenerative lumbar disc disease: in vivo data support the rationale for the selection of appropriate animal models

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