Lee Naomi N, Salzer Elias, Bach Frances C, Bonilla Andres F, Cook James L, Gazit Zulma, Grad Sibylle, Ito Keita, Smith Lachlan J, Vernengo Andrea, Wilke Hans-Joachim, Engiles Julie B, Tryfonidou Marianna A
Thompson Laboratory for Regenerative Orthopaedics University of Missouri Columbia Missouri USA.
Orthopaedic Biomechanics, Department of Biomedical Engineering Eindhoven University of Technology Eindhoven The Netherlands.
JOR Spine. 2021 Jun 14;4(2):e1162. doi: 10.1002/jsp2.1162. eCollection 2021 Jun.
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.
涉及大型动物模型的临床前研究旨在尽可能重现临床情况，并弥合从实验台到病床边的差距。迄今为止，在大型动物模型中研究椎间盘（IVD）退变和再生的研究已经采用了广泛的方法来进行结果评估。本文旨在整合关于IVD退变大型动物临床前模型的现有知识、专业技能和经验，以创建一个包含解剖学和功能结果的综合工具箱。在此，我们提出一种基于三个尺度的大型动物IVD评分算法：宏观尺度（大体形态、影像学和生物力学）、微观尺度（组织学、生物化学和生物分子分析）和临床尺度（神经状态、活动能力和疼痛）。所提出的算法包括对所有三个尺度的逐步评估，包括脊柱疼痛评估以及IVD健康和疾病的相关结构和功能成分。这个综合工具箱是为四种常用的临床前大型动物模型（狗、猪、山羊和绵羊）设计的，以促进标准化和适用性。此外，它旨在便于跨研究进行比较，同时在结果背景下辨别物种之间的相关差异，目标是提高兽医临床相关性。本文突出了当前IVD再生临床前大型动物模型中的主要挑战，并讨论了对未来方向的见解，这些见解可能会增进对潜在病理学的理解。因此，IVD研究界可以加深对IVD退变和再生过程中发生的分子、细胞、结构和生物力学变化的探索，为临床相关治疗策略铺平道路。
