Anti-inflammatory Cell Based Repair of Intervertebral Disc Degeneration

基于抗炎细胞的椎间盘退变修复

• 批准号: 10861338
• 负责人: NADEEN O. CHAHINE
• 金额: $ 49.41万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10861338
• 关键词: Address; Afferent Neurons; Anti-Inflammatory Agents; Area; Award; Back Pain; Catalogs; Cell Shape; Cells; Disease; Future; Goals; Growth; Hyperalgesia; Inflammation; Inflammatory; Inflammatory Response; Injury; Intervertebral disc structure; Maps; Mesenchymal Stem Cells; Methodology; Molecular Profiling; Musculoskeletal; Musculoskeletal Diseases; Nerve; Neurons; Pain; Pain Research; Pain Threshold; Parents; Pathologic; Patient-Focused Outcomes; Phenotype; Population; Rattus; Sensory; Symptoms; Work; afferent nerve; bone marrow mesenchymal stem cell; conventional therapy; cytokine; disability; discogenic pain; improved outcome; injured; innovation; interest; intervertebral disk degeneration; nerve supply; neural; novel marker; novel therapeutics; pain sensation; pain sensitivity; patient subsets; regenerative therapy; repaired; response; spinal disk injury; stem cell therapy

Project Abstract Discogenic back pain, is a leading cause of disability, and involves degenerative changes of the intervertebral disc (IVD), including matrix degradation, altered cell shape and phenotype, inflammation, and pathological nerve ingrowth. Since only a small subset of patients responds favorably to conventional treatments which address the symptoms but not the disease, there is a need for new therapies to treat disc degeneration (DD). Pro-inflammatory cytokines, which are associated with painful DD, lower the threshold for pain and lead to an exaggerated pain response or increased pain sensitivity (hyperalgesia). In the parent award, we are identifying strategies to reduce the pro-inflammatory and enhance the anti-inflammatory responses of bone marrow derived MSCs treatment for IVD repair. Therefore, the goal of this project is to examine ‘bidirectional interaction between injured painful IVD and sensory nerves’, an area of interest described in NOT-AR-23-015. The goal of this project is to define the innervation and phenotype of the sensory neurons innervating the caudal IVD, and to assess changes in the DRGs of the innervating neurons with injury and mesenchymal stem cell (MSC) treatment. This project meets Goal A, to generate supporting evidence towards a future innovative study and new scientific direction in pain research in musculoskeletal diseases. Aim S1 studies will spatially map the sensory neural innervation of the rat caudal IVD. Aim S2 studies will identify changes in the molecular signatures of DRG populations and DRG sensitization with caudal IVD injury and anti- inflammatory cell treatment. This project will stimulate substantial innovations on pain research approaches and methodologies. Completion of this work will provide markers for new, functionally distinct sensory neurons relevant to painful IVDs. The resulting catalog will also illustrate the diversity of sensory types and the cellular complexity underlying painful sensation due to musculoskeletal degeneration, injury and treatment.

项目摘要 椎间盘源性背痛是残疾的主要原因，涉及椎间盘的退行性变化。 椎间盘（IVD），包括基质降解，改变的细胞形状和表型， 炎症和病理性神经长入。由于只有一小部分患者对 虽然传统治疗方法只能解决症状而不能解决疾病，但需要新的治疗方法， 治疗椎间盘退变（DD）。与疼痛性DD相关的促炎细胞因子降低了 疼痛阈值，并导致疼痛反应过度或疼痛敏感性增加（痛觉过敏）。在 家长奖，我们正在确定战略，以减少促炎和加强抗炎 骨髓来源的MSC治疗对IVD修复的反应。因此，本项目的目标是 检查“受伤的疼痛IVD和感觉神经之间的双向相互作用”，这是一个感兴趣的领域， 在NOT-AR-23-015中。本计画的目标是要明确感觉神经元的神经支配和表现型 神经支配尾侧IVD，并评估损伤后神经支配神经元DRG的变化， 间充质干细胞（MSC）治疗。该项目符合目标A，即为以下目标提供支持证据： 一个未来的创新研究和新的科学方向，在疼痛研究的肌肉骨骼疾病。目标S1 研究将在空间上绘制大鼠尾侧IVD的感觉神经支配。目的S2研究将确定 DRG群体分子特征的变化以及尾侧IVD损伤和抗- 炎症细胞治疗。该项目将刺激疼痛研究方法的实质性创新， 方法论。这项工作的完成将为新的、功能不同的感觉神经元提供标记 与疼痛的体外受精相关。由此产生的目录还将说明感觉类型和细胞的多样性。 由于肌肉骨骼退化、损伤和治疗引起的潜在疼痛感的复杂性。

项目成果

An in vivo model of ligamentum flavum hypertrophy from early-stage inflammation to fibrosis.

• DOI: 10.1002/jsp2.1260
• 发表时间: 2023-09
• 期刊: JOR SPINE
• 影响因子: 3.7
• 作者: Burt, Kevin G.;Viola, Dan C.;Lisiewski, Lauren E.;Lombardi, Joseph M.;Amorosa, Louis F.;Chahine, Nadeen O.
• 通讯作者: Chahine, Nadeen O.