Cell Therapy for the degenerating intervertebral discs

退变椎间盘细胞疗法

• 批准号: 8010767
• 负责人: YEJIA ZHANG
• 金额: $ 5万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010767
• 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 Plans; Diagnostic radiologic examination; Environment; Enzyme-Linked Immunosorbent Assay; Etiology; Excision; 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; 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; Training; Training Programs; Transduction Gene; Transplantation; United States; Universities; Vertebral column; Weight; Work; abstracting; aggrecan; aging population; base; bone morphogenetic protein 7; career; career development; cost; density; design; economic impact; experience; gene therapy; human osteogenic protein 1; in vivo; indexing; injured; interest; intervertebral disk degeneration; meetings; programs; repaired; research and development; socioeconomics; 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.

学员是一名年轻的内科医生，具有很强的基础科学背景。在国际足联的指导下 康复科学家培训计划(RMSTP)，她设计了一条职业道路，将她 科学和临床方面的兴趣。她的研究在《纽约时报》上引起了相当多的积极关注。 康复领域。这项工作产生了七份完整的手稿：三份已经出版，一份在 按(见所附手稿和信函)，其中三个正在审查中。此外，还发表了15篇摘要 在国家和国际会议上介绍。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长，成为独立的 临床医生兼调查员。 学员的研究计划解决了一个极其重要的临床问题--背部疼痛。尽管 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。 与背部疼痛有关。使用生长因子的生物治疗可能会促进基质修复和恢复 生理功能。以细胞为基础的基因疗法，旨在持续释放生长因子，将 被探索。 这项修订后的提案包含了进一步支持中心假设的新数据，即细胞疗法可能会 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) 注射转导Ad-hBMP-7的同种异体兔关节软骨细胞的外植体产生更多 HBMP-7蛋白；II)兔IVD组织内注射表达hBMP-7的关节软骨细胞后积聚 更多的蛋白多糖。基于这些发现，她提议研究BMP-7对退行性变的影响 兔腰椎间盘采用体外基因转移法。她还在体内进行了一次试验 同种异体兔关节软骨细胞移植入变性兔IVD模型的研究 展示了她进行活体研究的能力。 椎间盘生物学家欧文·夏皮罗博士承担了她的主要导师的角色。实习生的活体研究 还将得到脊柱外科医生D·格雷格·安德森博士的帮助，他在动物椎间盘方面拥有丰富的经验 损伤模型。在修订的培训计划中，学员建议参加课程工作并学习 其他技术。托马斯·杰斐逊大学提供了丰富的环境，并拥有强大的 承诺支持她的职业发展。

项目成果

Fibronectin splice variation in human knee cartilage, meniscus and synovial membrane: observations in osteoarthritic knee.

• DOI: 10.1002/jor.22787
• 发表时间: 2015-04
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Scanzello CR;Markova DZ;Chee A;Xiu Y;Adams SL;Anderson G;Zgonis M;Qin L;An HS;Zhang Y
• 通讯作者: Zhang Y

Biological treatment for degenerative disc disease: implications for the field of physical medicine and rehabilitation.

• DOI: 10.1097/phm.0b013e31817c1945
• 发表时间: 2008-09
• 期刊: American journal of physical medicine & rehabilitation
• 影响因子: 3
• 作者: Yejia Zhang;H. An;C. Tannoury;E. Thonar;M. Freedman;D. Anderson

Cell therapy using articular chondrocytes overexpressing BMP-7 or BMP-10 in a rabbit disc organ culture model.

在兔椎间盘器官培养模型中使用过表达 BMP-7 或 BMP-10 的关节软骨细胞进行细胞治疗。

• DOI: 10.1097/brs.0b013e31816b1f38
• 发表时间: 2008
• 期刊: Spine
• 影响因子: 3
• 作者: Zhang,Yejia;Phillips,FrankM;Thonar,EugeneJ-MA;Oegema,Theodore;An,HowardS;Roman-Blas,JorgeA;He,Tong-Chuan;Anderson,DGreg
• 通讯作者: Anderson,DGreg

Histological features of the degenerating intervertebral disc in a goat disc-injury model.

• DOI: 10.1097/brs.0b013e3181f60b39
• 发表时间: 2011-09-01
• 期刊: Spine
• 影响因子: 3
• 作者: Zhang Y;Drapeau S;An HS;Markova D;Lenart BA;Anderson DG
• 通讯作者: Anderson DG

Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc: a novel cell source for disc repair.

培养的兔椎间盘中的人脐带血液衍生的间充质干细胞：椎间盘修复的新细胞来源。

• DOI: 10.1097/phm.0b013e31825f148a
• 发表时间: 2013-05
• 期刊: American journal of physical medicine & rehabilitation
• 影响因子: 3
• 作者: Anderson DG;Markova D;An HS;Chee A;Enomoto-Iwamoto M;Markov V;Saitta B;Shi P;Gupta C;Zhang Y
• 通讯作者: Zhang Y