Cell Therapy for the degenerating intervertebral discs

退变椎间盘细胞疗法

• 批准号: 7687031
• 负责人: YEJIA ZHANG
• 金额: $ 4.65万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-20 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687031
• 关键词: Address; Adenoviruses; Allogenic; Animals; Attention; Back Pain; Basic Science; Biochemical; Biological; Bone Morphogenetic Proteins; Cell Count; Cell Survival; Cell Therapy; Cells; Chondrocytes; Clinical; Collagen; Collagen Type II; Control Groups; Data; Development; Diagnostic radiologic examination; Economics; Environment; Enzyme-Linked Immunosorbent Assay; Etiology; Excision; Expression Feature; Fluorescence Microscopy; Gene Transfer; Genes; Green Fluorescent Proteins; Growth Factor; Height; Homeostasis; Image; In Vitro; Injection of therapeutic agent; Injury; International; Intervertebral disc structure; Learning; Letters; Magnetic Resonance Imaging; Maintenance; Manuscripts; Medical; Mentors; Methods; Modeling; Numbers; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome Measure; Phenotype; Physicians; Physiological; Production; Proteins; Proteoglycan; Protons; Publishing; Puncture procedure; Rehabilitation therapy; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Scientist; Seasons; Surgeon; Technical Expertise; Techniques; Tissues; Today; Training; Training Programs; Transduction Gene; Transplantation; United States; Universities; Vertebral column; Week; Weight; Work; abstracting; aggrecan; aging population; base; bone morphogenetic protein 7; career; cost; density; design; experience; gene therapy; human osteogenic protein 1; in vivo; indexing; injured; interest; intervertebral disk degeneration; programs; repaired; research and development; tool

DESCRIPTION (provided by applicant): The trainee is a young physician with a strong basic science background. With the guidance of the rehabilitation scientist training program (RMSTP), she has designed a career path that brings together her scientific and clinical interests. Her research has attracted a considerable amount of positive attention in the field of rehabilitation. Seven full manuscripts resulted from this work: three have been published, one in press (see attached manuscript and letter), and three are in review. In addition, 15 abstracts have been presented at national and international meetings. The proposed research development plan will allow her to gain additional technical expertise under the guidance of seasoned scientists, and become an independent clinician-investigator. The trainee's research plan addresses an immensely important clinical problem, back pain. Although the etiology of back pain is most likely multi-factorial, intervertebral disc degeneration is perhaps causally associated with back pain. Biological treatment with a growth factor may promote matrix repair and restore physiological function. Cell-based gene therapy, which aims at the sustained release of growth factors, will be explored. This revised proposal contains new data further supporting the central hypothesis that cell therapy is likely to represent an effective tool for slowing or even reversing disc degeneration (1) Rabbit intervertebral disc (IVD) explants injected with allogenic rabbit articular chondrocytes transduced with Ad-hBMP-7 produce more hBMP-7 protein, and (2) Rabbit IVD explants injected with articular chondrocytes expressing hBMP-7 accumulate more proteoglycans. Based on these findings, the trainee proposes to study the effects of BMP-7 on degenerative rabbit intervertebral discs using the ex vivo gene transfer method. She has also performed a pilot in vivo study and transplanted allogenic rabbit articular chondrocytes into the degeneration rabbit IVD, demonstrating her ability to perform in vivo studies. Dr. Irving Shapiro, a disc biologist, has assumed the role of the trainee's primary mentor. Her in vivo study will also be helped by Dr. D. Greg Anderson, a spine surgeon, with extensive experience with the animal disc injury model. In the revised training plan, the trainee proposes to participate in course work and to learn additional techniques. Thomas Jefferson University provides a rich environment, and has a strong commitment to support her career development.

描述（由申请人提供）： 受训者是一位具有深厚基础科学背景的年轻医生。在康复科学家培训计划（RMSTP）的指导下，她设计了一条将她的科学和临床兴趣结合起来的职业道路。她的研究在康复领域引起了相当多的积极关注。这项工作产生了七份完整的手稿：三份已出版，一份正在印刷（见所附手稿和信件），三份正在审查中。此外，15 篇摘要已在国内和国际会议上发表。拟议的研究发展计划将使她能够在经验丰富的科学家的指导下获得额外的技术专业知识，并成为一名独立的临床医生研究员。 实习生的研究计划解决了一个非常重要的临床问题：背痛。尽管背痛的病因很可能是多因素的，但椎间盘退变可能与背痛有因果关系。生长因子的生物治疗可以促进基质修复并恢复生理功能。将探索旨在持续释放生长因子的细胞基因疗法。 该修订提案包含进一步支持中心假设的新数据，即细胞疗法可能代表减缓甚至逆转椎间盘退变的有效工具（1）注射用Ad-hBMP-7转导的同种异体兔关节软骨细胞的兔椎间盘（IVD）外植体产生更多的hBMP-7蛋白，以及（2）注射关节软骨的兔IVD外植体 表达 hBMP-7 的软骨细胞积累更多的蛋白聚糖。基于这些发现，学员提出利用离体基因转移方法研究BMP-7对退变兔椎间盘的影响。她还进行了一项试点体内研究，并将同种异体兔关节软骨细胞移植到变性兔 IVD 中，证明了她进行体内研究的能力。 椎间盘生物学家 Irving Shapiro 博士担任了学员的主要导师。她的体内研究也将得到脊柱外科医生 D. Greg Anderson 博士的帮助，他在动物椎间盘损伤模型方面拥有丰富的经验。在修订后的培训计划中，学员建议参加课程作业并学习额外的技术。托马斯杰斐逊大学提供了丰富的环境，并坚定地致力于支持她的职业发展。