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 背痛是全世界残疾的最常见原因，椎间盘突出症是 一个主要原因。尽管椎间盘突出症和背痛的临床意义，没有有效的 治疗目前可用。由于在椎间盘研究方面的巨大努力， 是椎间盘突出后背痛和腿痛的关键因素。然而，疝气之间的动态相互作用 由于可用于解开这种复杂性的研究工具有限，因此对椎间盘和免疫细胞的了解很少。 为了解决这些知识和技术差距，我们将利用我们在活组织培养和活组织培养方面的专业知识， 组织染色和成像技术，以建立一种新的人椎间盘炎组织切片培养模型 组织（椎间盘突出伴炎性组织）。这个项目的目标是重新获得病理性的 椎间盘突出的环境，并最终发现和验证新的生物标志物。在这次探索中 生物工程研究项目，我们将建立第一个人类炎症椎间盘组织切片培养系统 对炎症刺激和抗炎治疗有反应（目的1），并概括了 在长期3周培养中的体内炎症微环境（Aim 2）。如果成功，该项目将提供一个 新的离体模型，以阐明椎间盘突出和炎症级联反应之间的复杂病理学。 当完成后，这个多功能的文化和分析系统将很容易应用于推进机械 了解椎间盘疾病和一系列其他肌肉骨骼疾病，包括骨关节炎， 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

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

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