An ex vivo system to model the inflammatory microenvironment of human disc herniation

模拟人类椎间盘突出炎症微环境的离体系统

• 批准号: 10302594
• 负责人: XUDONG J. LI
• 金额: $ 38.82万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302594
• 关键词: Acute; Address; Affect; Animal Model; Animals; Anti-Inflammatory Agents; Antibodies; Back Pain; Biochemical; Biological Assay; Biological Markers; Biological Models; Biology; Biomedical Engineering; Cell Culture Techniques; Cell Nucleus; Cell Survival; Cell physiology; Cells; Clinical Trials; Coculture Techniques; Complex; Degenerative polyarthritis; Disease; Dose; Dyes; Environment; Enzyme-Linked Immunosorbent Assay; Evaluation; Fluorescence; Fresh Tissue; Goals; Health; Hernia; Human; Human Pathology; Image; Imaging technology; Immune; Immune response; In Situ; In Vitro; Infiltration; Inflammation; Inflammatory; Inflammatory Infiltrate; Injury; Intervertebral disc structure; Knowledge; Label; Mediator of activation protein; Methods; Microfluidic Microchips; Microfluidics; Modeling; Monitor; Mus; Musculoskeletal; Musculoskeletal Diseases; Neurosciences Research; Nutrient; Organ Culture Techniques; Outcome; Oxygen; Pain; Pain in lower limb; Pain management; Pathologic; Pathology; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Population; Research; Research Project Grants; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Site; Slice; Slipped Disk; Stimulus; Structure; System; Systems Analysis; TNF gene; Technology; Tendinopathy; Therapeutic; Time; Tissue Harvesting; Tissue Stains; Tissue imaging; Tissues; anticancer research; clinically significant; confocal imaging; cytokine; disability; efficacious treatment; experimental study; human model; improved; in vivo; intervertebral disk degeneration; macrophage; monocyte; novel; novel therapeutics; recruit; response; time use; tissue culture; tool; tumor-immune system interactions

Project Summary Back pain is the most common contributor of disability worldwide, with intervertebral disc herniation being a leading cause. Despite the clinical significance of intervertebral disc herniation and back pain, no efficacious treatment is currently available. Thanks to the tremendous efforts in disc research, inflammation is recognized as a key player for back and leg pain after disc herniation. However, the dynamic interplay between herniated discs and immune cells is poorly understood due to limited research tools available to unravel such complexity. To address these knowledge and technology gaps, we will leverage our expertise in live tissue culture and live tissue staining and imaging technologies to develop a novel tissue slice culture model of human inflamed disc tissue (herniated discs with inflammatory tissues). The goal of this project is to recapture the pathological environment of the herniated disc and ultimately discover and validate new biomarkers. In this Exploratory Bioengineering Research project, we will establish the first slice culture system for human inflamed disc tissue that responds to inflammatory stimuli and anti-inflammatory therapies (Aim 1) and recapitulates the complex in vivo inflammatory microenvironment in long-term 3-week culture (Aim 2). If successful, this project will provide a novel ex vivo model to elucidate the complex pathology between the herniated disc and inflammatory cascade. When completed, this versatile culture and analysis system will be readily applied to advance the mechanistic understanding of the disc disease and a range of other musculoskeletal disorders, including osteoarthritis and tendonitis.

项目摘要 背痛是全球残疾的最常见贡献者，椎间盘椎间盘突出症是 主要原因。尽管椎间盘催眠和背痛的临床意义，但没有有效的 目前可获得治疗。多亏了椎间盘研究所做的巨大努力，炎症得到了认可 作为椎间盘突出症后背部和腿部疼痛的关键球员。但是，椎骨之间的动态相互作用 椎间盘和免疫细胞由于可用的研究工具有限而无法理解这种复杂性。 为了解决这些知识和技术差距，我们将利用我们在活组织文化中的专业知识并生活 组织染色和成像技术，以开发一种新型的人类发炎的组织切片培养模型 组织（带有炎症组织的椎间盘椎间盘）。该项目的目的是重新夺回病理 椎间盘理学的环境，最终发现并验证新的生物标志物。在此探索性中 生物工程研究项目，我们将建立第一个针对人类发炎盘组织的切片培养系统 这对炎症刺激和抗炎疗法有反应（AIM 1），并概括了复合物 长期3周培养中的体内炎症微环境（AIM 2）。如果成功，该项目将提供 新型的离体模型，以阐明椎间盘突出和炎症性级联反应之间的复杂病理。 完成后，这种多功能文化和分析系统将很容易应用以提高机械 了解椎间盘疾病以及其他一系列其他肌肉骨骼疾病，包括骨关节炎和 肌腱炎。

项目成果

Heterogeneous macrophages contribute to the pathology of disc herniation induced radiculopathy.

异质巨噬细胞导致椎间盘突出引起的神经根病的病理学。

• DOI: 10.1016/j.spinee.2021.10.014
• 发表时间: 2022-04
• 期刊: The spine journal : official journal of the North American Spine Society
• 作者: Jin L;Xiao L;Ding M;Pan A;Balian G;Sung SJ;Li XJ
• 通讯作者: Li XJ

Single-cell assessment of the modulation of macrophage activation by ex vivo intervertebral discs using impedance cytometry.

• DOI: 10.1016/j.bios.2022.114346
• 发表时间: 2022-08-15
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6

Amine Functionalized Trimetallic Nitride Endohedral Fullerenes: A Class of Nanoparticle to Tackle Low Back/Leg Pain.

• DOI: 10.1021/acsabm.2c00269
• 发表时间: 2022-06-20
• 期刊: ACS APPLIED BIO MATERIALS
• 影响因子: 4.7
• 作者: Xiao, Li;Huang, Rong;Sulimai, Nurul;Yao, Ricky;Manley, Brock;Xu, Peng;Felder, Robin;Jin, Li;Dorn, Harry C;Li, Xudong
• 通讯作者: Li, Xudong