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.

实习生是一位具有深厚基础科学背景的年轻医生。在该机构的指导下 康复科学家培训计划（RMSTP），她设计了一条职业道路，将她聚集在一起 科学和临床兴趣。她的研究引起了学术界的广泛关注 康复领域。这项工作产生了七份完整手稿：三份已出版，一份已出版 出版社（见所附手稿和信件），其中三篇正在审查中。此外，还发表了 15 篇摘要。 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，并成为独立的 临床医生-研究者。 实习生的研究计划解决了一个非常重要的临床问题：背痛。虽然 背痛的病因很可能是多因素的，椎间盘退变可能是因果关系 与背痛有关。生长因子的生物治疗可以促进基质修复和恢复 生理功能。基于细胞的基因疗法旨在持续释放生长因子，将 被探索。 该修订后的提案包含进一步支持细胞疗法可能的中心假设的新数据 是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 hBMP-7蛋白； ii) 注射表达 hBMP-7 的关节软骨细胞的兔 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 对退行性病变的影响 使用离体基因转移方法制备兔椎间盘。她还进行了体内试验 研究并将同种异体兔关节软骨细胞移植到变性兔IVD中， 展示了她进行体内研究的能力。 椎间盘生物学家欧文·夏皮罗博士担任了她的主要导师。实习生的体内研究 还将得到脊柱外科医生 D. Greg Anderson 博士的帮助，他在动物椎间盘方面拥有丰富的经验 伤害模型。在修订后的培训计划中，学员提出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，并拥有强大的 致力于支持她的职业发展。

项目成果

Fibronectin splicing variants in human intervertebral disc and association with disc degeneration.

人椎间盘中的纤连蛋白剪接变异及其与椎间盘退变的关联。

• 发表时间: 2010-08-01
• 影响因子: 3
• 作者: Anderson, D Greg;Markova, Dessislava;Adams, Sherrill L;Pacifici, Maurizio;An, Howard S;Zhang, Yejia
• 通讯作者: Zhang, Yejia

Treatment of primary basilar invagination by cervical traction and posterior instrumented reduction together with occipitocervical fusion.

通过颈椎牵引和后路器械复位结合枕颈融合术治疗原发性颅底凹陷症。

• 发表时间: 2011-09-01
• 影响因子: 3
• 作者: Peng, Xinsheng;Chen, Liyan;Wan, Yong;Zou, Xuenong
• 通讯作者: Zou, Xuenong

Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc.

退变人类椎间盘中的纤连蛋白片段和裂解酶 ADAM-8。

• 发表时间: 2014-07-15
• 影响因子: 3
• 作者: Ruel, Nancy;Markova, Dessislava Z;Adams, Sherrill L;Scanzello, Carla;Cs;Gerard, David;Shi, Peng;Anderson, D Greg;Zack, Marc;An, Howard S;Chen, Di;Zhang, Yejia
• 通讯作者: Zhang, Yejia

Biglycan Inhibits Capsaicin-Induced Substance P Release by Cultured Dorsal Root Ganglion Neurons.

Biglycan 抑制培养的背根神经节辣椒素诱导的 P 物质释放。

• 发表时间: 2016-09
• 影响因子: 3
• 作者: Shi, Peng;Chen, Er;Cs;Chee, Ana;Tannoury, Chadi;Qin, Ling;Lin, Han;An, Steven;An, Howard S;Zhang, Yejia
• 通讯作者: Zhang, Yejia

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来源的间充质干细胞：用于椎间盘修复的新型细胞来源。

• 发表时间: 2013-05
• 影响因子: 3
• 作者: Anderson, D Greg;Markova, Dessislava;An, Howard S;Chee, Ana;Enomoto;Markov, Vladimir;Saitta, Biagio;Shi, Peng;Gupta, Chander;Zhang, Yejia
• 通讯作者: Zhang, Yejia