Notochordal Cell Derived Therapies for Painful Disc Degeneration

 描述（由申请人提供）：椎间盘（IVD）退变是一种与腰痛发病机制相关的衰弱性疾病，相关费用每年可能超过1000亿美元。该奖项的总体目标是开发新型治疗药物和策略，以微创方式使用，以限制退变，恢复IVD结构，并减少退行性椎间盘疾病的疼痛状况。我们的第1年母基金的初步数据突出了蛋白聚糖结构和硫酸化模式在抑制神经血管侵入IVD的线索中的至关重要的作用。尽管蛋白聚糖在IVD基质中非常重要，但多年来在糖胺聚糖（GAG）结构和硫酸化模式的表征方面尚未取得重大进展。该BIRT为IVD研究领域引入了新技术，这些技术允许对蛋白聚糖进行表征，而不仅仅是GAG含量测量，还包括发挥重要生物活性作用的特征。BIRT的这一建议发展了西奈山的James Iatridis博士和伦斯勒理工学院的Robert Linhardt博士之间的新合作。我们将联合收割机在IVD研究方面的专业知识与蛋白聚糖专家相结合，以开发和应用新技术来表征和分离IVD中的GAG。我们认为，IVD和软骨的研究是缓慢的蛋白聚糖的特点，其糖胺聚糖（GAG）含量单独。蛋白聚糖的结构或硫酸化模式负责许多重要的生物活性作用，包括神经血管生长。目的1是使用人类尸检样本和椎间盘切除术期间疼痛性IVD的手术样本，表征IVD区域中生长、老化和疾病的人IVD的GAG特征。目的2是使用细胞培养模型表征从人IVD中分离的不同GAG结构（CS4、CS6、KS和DS）对神经血管生长的影响。这个项目是重要的，因为GAG结构和硫酸化模式在软骨组织中探索不足，这些概念与椎间盘源性背痛问题高度相关。该方法是创新的，因为它包括先进的糖组学测量。传播里程碑包括向RPI和西奈山的研究生教授这些新技术，并在国际研究会议上向IVD研究人员介绍这些技术和新科学。

 DESCRIPTION (provided by applicant): Intervertebral disc (IVD) degeneration is a debilitating disorder implicated in the pathogenesis of low back pain with associated costs that can exceed $100 billion annually. The overall goal of the parent award is to develop novel therapeutic agents and strategies for use in a minimally invasive manner to limit degeneration, restore IVD structure, and reduce painful conditions of degenerative disc disease. Our year 1 preliminary data of the parent grant highlight the crucially important role of proteoglycan structure and sulfation pattern in cues to inhibit neurovascular invasion into the IVD. As important as proteoglycans are in the IVD matrix, there has not been a major advance in the characterization of glycosaminoglycan (GAG) structure and sulfation patterns in many years. This BIRT introduces new technologies to the IVD research field that allow characterization of proteoglycans, beyond GAG content measurements, to include features that play important bioactive roles. This BIRT proposal develops a new collaboration between Dr. James Iatridis at Mount Sinai and Dr. Robert Linhardt at Rensselaer Polytechnic Institute. We combine expertise in IVD research with a proteoglycan expert in order to develop and apply novel techniques for the characterization and isolation of GAGs in the IVD. We believe that IVD and cartilage research is slowed by the characterization of proteoglycans by their glycosaminoglycan (GAG) content alone. The structure or sulfation patterns of proteoglycans are responsible for many important bioactive roles including neurovascular growth. Aim 1 is to characterize the GAG profile of human IVDs with growth, aging and disease across IVD regions using human autopsy samples and surgical samples from painful IVDs during discectomy surgery. Aim 2 is to characterize the effects of different GAG structures (CS4, CS6, KS& DS) that are isolated from human IVDs on neurovascular growth using cell culture models. This project is significant because the GAG structure and sulfation patterns are underexplored in cartilaginous tissues and these concepts are highly relevant to the problem of discogenic back pain. The approach is innovative because it includes advanced glycomics measurements. Dissemination milestones involve teaching these novel technologies to graduate students at both RPI and Mount Sinai and also introducing these techniques and new science to IVD researchers at an international research meeting.