Journal
JOR SPINE
Volume 4, Issue 2, Pages -Publisher
WILEY
DOI: 10.1002/jsp2.1162
Keywords
biomechanical testing; clinical assessment; disc disease; dog; goat; histopathology; intervertebral disc; low back pain; neck pain; pig; sheep; spine disorders; spine research
Categories
Funding
- AO Foundation [AO-03-W16]
- Foundation for the National Institutes of Health [R01AR066517, R01AR077435, OD011126]
- Fulbright Association
- German Research Council [DFG Wi 1352/14-3]
- H2020 Societal Challenges [825925]
- ReumaNederland [LLP22]
- US Department of Veteran's Affairs [I01RX001321]
- H2020 Societal Challenges Programme [825925] Funding Source: H2020 Societal Challenges Programme
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Preclinical studies involving large animal models aim to bridge the gap between benchtop and bedside by replicating the clinical situation. This paper consolidates knowledge and expertise in large animal preclinical models of intervertebral disc degeneration, presenting a scoring algorithm based on macroscopic, microscopic, and clinical scales. Challenges and future directions in large animal models for IVD regeneration are discussed to pave the way for clinically relevant therapeutic strategies.
Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes. Herein, we present a Large Animal IVD Scoring Algorithm based on three scales: macroscopic (gross morphology, imaging, and biomechanics), microscopic (histological, biochemical, and biomolecular analyses), and clinical (neurologic state, mobility, and pain). The proposed algorithm encompasses a stepwise evaluation on all three scales, including spinal pain assessment, and relevant structural and functional components of IVD health and disease. This comprehensive tool box was designed for four commonly used preclinical large animal models (dog, pig, goat, and sheep) in order to facilitate standardization and applicability. Furthermore, it is intended to facilitate comparison across studies while discerning relevant differences between species within the context of outcomes with the goal to enhance veterinary clinical relevance as well. Current major challenges in pre-clinical large animal models for IVD regeneration are highlighted and insights into future directions that may improve the understanding of the underlying pathologies are discussed. As such, the IVD research community can deepen its exploration of the molecular, cellular, structural, and biomechanical changes that occur with IVD degeneration and regeneration, paving the path for clinically relevant therapeutic strategies.
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