Cell Therapy for the degenerating intervertebral discs

退变椎间盘细胞疗法

• 批准号: 7342105
• 负责人: YEJIA ZHANG
• 金额: $ 8.31万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342105
• 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; Low Back Pain; 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

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: i) Rabbit intervertebral disc (IVD) explants injected with allogenic rabbit articular chondrocytes transduced with Ad-hBMP-7 produce more hBMP-7 protein; ii) Rabbit IVD explants injected with articular chondrocytes expressing hBMP-7 accumulate more proteoglycans. Based on these findings, she 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 her primary mentor. The trainee's 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.

受训者是一位年轻的内科医生，有很强的基础科学背景。为指导 康复科学家培训计划（RMSTP），她设计了一个职业道路，汇集了她 科学和临床兴趣。她的研究在世界范围内引起了相当多的积极关注。 康复领域。七个完整的手稿产生了这项工作：三个已出版，一个在 出版社（见所附手稿和信件），三个在审查。此外，15份摘要已 在国家和国际会议上发言。拟议的研究开发计划将使她能够 在经验丰富的科学家的指导下获得额外的技术专长，并成为一个独立的 临床研究员。 受训者的研究计划针对一个极其重要的临床问题，背痛。虽然 背痛的病因很可能是多因素的，椎间盘退变可能是原因之一。 与背痛有关。用生长因子进行生物处理可以促进基质修复和恢复 生理功能以细胞为基础的基因治疗，其目的是持续释放生长因子， 被探索。 这项修订后的提案包含了进一步支持核心假设的新数据，即细胞疗法可能 代表了减缓甚至逆转椎间盘退变的有效工具：i）兔椎间盘（IVD） 注射Ad-hBMP-7转导的同种异体兔关节软骨细胞的外植体产生更多的 hBMP-7蛋白; ii）用表达hBMP-7的关节软骨细胞注射的兔IVD外植体积聚 更多的蛋白多糖基于这些发现，她建议研究BMP-7对退行性变的影响。 使用离体基因转移方法的兔椎间盘。她还进行了一个试点在体内 研究并将同种异体兔关节软骨细胞移植到退变兔椎间盘内， 证明了她进行体内研究的能力。 博士椎间盘生物学家欧文·夏皮罗（Irving Shapiro）担任了她的主要导师。受训者的体内研究 也将得到D博士的帮助。格雷格安德森，脊柱外科医生，具有丰富的经验，与动物椎间盘 损伤模型在修订后的培训计划中，受训者提出参加课程工作， 其他技术。托马斯杰斐逊大学提供了一个丰富的环境，并有强大的 支持其职业发展。