Anti-inflammatory Cell Based Repair of Intervertebral Disc Degeneration

项目摘要 关节盘源性背痛是致残的主要原因之一，涉及腰椎退行性改变。 间盘(IVD)，包括基质降解、细胞形态和表型改变， 炎症和病理性神经生长。因为只有一小部分患者对 传统的治疗方法是针对症状而不是疾病，因此需要新的治疗方法 治疗椎间盘退行性变(DD)。与疼痛的DD相关的促炎细胞因子降低了 疼痛的阈值并导致疼痛反应的夸大或疼痛敏感性的增加(痛觉过敏)。在 家长奖，我们正在确定减少促炎和增强抗炎的策略 骨髓间充质干细胞对IVD修复的反应。因此，这个项目的目标是 研究“受伤的痛苦的IVD和感觉神经之间的双向相互作用”，描述了一个感兴趣的区域 在NOT-AR-23-015中。这个项目的目标是确定感觉神经元的神经支配和表型。 神经支配尾侧下丘脑室旁核，并评估神经损伤神经元DRG的变化 骨髓间充质干细胞(MSC)治疗。该项目符合目标A，以生成支持证据，以 肌肉骨骼疾病疼痛研究的未来创新研究和新的科学方向。目标S1 研究将对大鼠尾部IVD的感觉神经支配进行空间定位。AIM S2研究将确定 尾部IVD损伤和抗损伤对DRG群体分子特征和DRG致敏作用的影响 炎性细胞治疗。该项目将刺激疼痛研究方法和方法的实质性创新 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 与痛苦的静脉输卵管疾病有关。由此产生的目录还将说明感觉类型和细胞的多样性 肌肉骨骼退化、损伤和治疗引起的痛感的复杂性。

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.