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

点击翻译按钮获取中文摘要

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.