A BABOON MODEL OF DEGENERATIVE DISC DISEASE: A PILOT STUDY TO EVALUATE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 椎间盘是脊椎骨之间的软骨垫，允许运动。一个坚韧的纤维软骨外环围绕着内部充满水的中心形成椎间盘。 椎间盘是身体中最大的结构，没有血液供应。因此，受损或退化的椎间盘组织修复自身的能力非常有限。 据估计，仅在美国就有500万成年人患有慢性背部或颈部疼痛，主要是由于椎间盘退变。 目前还没有证实的狒狒腰椎间盘退变模型，研究一般仅限于急性损伤的正常脊柱。本研究旨在建立狒狒腰椎间盘退变模型。一个经过验证的模型将成为研究退行性椎间盘及其植入物（如动态稳定）和生物制剂（如水凝胶）治疗的宝贵工具。本研究的结果将用于确定最佳的手术技术和时间点，以产生轻度至中度退行性椎间盘疾病的人。据推测，适当的椎间盘损伤将诱导可重现的退行性反应，复制人类腰椎退行性椎间盘疾病。 文献报告了使用小鼠、大鼠、兔、绵羊、小型猪、猴和狒狒作为腰椎研究的体内模型。灵长类动物模型比绵羊模型更好地再现了直立脊柱的生物力学。与较小的哺乳动物相比，狒狒可能更好地复制人类脊柱的病理生理学，因为它的体积相对较大。事实上，狒狒的椎间盘表现出与人类相似的特征性退行性变模式。此外，人类和灵长类动物之间的遗传同源性也可能有助于使用免疫组织化学和基因芯片技术进行分析。 在这项初步研究中，六只狒狒将接受椎间盘手术，并在三个不同的水平上造成两种不同类型的损伤。将通过放射学和磁共振成像监测变性。 在研究结束时对狒狒实施安乐死后，将对脊柱进行组织学处理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vertebral discs are cushions of cartilage between each bone of the spine allowing for movement. An outer ring of tough fibrous cartilage that surrounds an inner water-filled center forms the discs. Discs are the largest structures in the body without a blood supply. Because of this, damaged or degenerated disc tissue is extremely limited in its ability to repair itself. An estimated 5 million adults in the US alone suffer with chronic back or neck pain primarily due to disc degeneration. There is no proven model for induced lumbar disc degeneration in the baboon, and research has generally been limited to normal spines with acute injury. This study will develop a degenerated lumbar disc model in the baboon. A proven model would become an invaluable tool for the study of the degenerated disc and its treatment with implants like dynamic stabilization and biologics like hydrogels. The results of this study will be used to determine that surgical technique and time point which best produce mild-to-moderate degenerative disc disease in people. It is hypothesized that an appropriate injury to the disc will induce a reproducible degenerative response that replicates degenerative disc disease in the human lumbar spine. The literature reports the use of mice, rats, rabbits, sheep, minipigs, monkeys, and baboons as in vivo models for study of the lumbar spine. The primate model better reproduces the biomechanics of an erect spine than the sheep model. Compared to smaller mammals, the baboon may better reproduce the pathophysiology of the human spine because of its relatively large size. In fact, the intervertebral disc of the baboon demonstrates characteristic patterns of degeneration similar to those in humans. Additionally, genetic homology between humans and primates may also facilitate analyses using immunohistochemical and gene chip technologies. In this pilot study, six baboons will undergo disc surgery and two different types of injury will be caused at three different levels. The degeneration will be monitored with radiological and magnetic resonance imaging. After the baboons are euthanized at the end of the study, the spines will be processed for histology.