Cell Therapy for the degenerating intervertebral discs

描述（由申请人提供）：受训者是一名年轻的医生，具有很强的基础科学背景。在康复科学家培训计划（RMSTP）的指导下，她设计了一条职业道路，将她的科学和临床兴趣结合在一起。她的研究在康复领域引起了相当多的积极关注。七个完整的手稿产生了这项工作：三个已出版，一个在印刷（见所附手稿和信件），三个在审查。此外，在国家和国际会议上提交了15份摘要。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，并成为一名独立的临床研究人员。 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，但椎间盘退变可能与背痛有因果关系。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。将探索以细胞为基础的基因治疗，其目的是持续释放生长因子。 该修订的提议包含进一步支持核心假设的新数据，即细胞疗法可能代表减缓或甚至逆转椎间盘退变的有效工具（1）用Ad-hBMP-7转导的同种异体兔关节软骨细胞注射的兔椎间盘（IVD）外植体产生更多的hBMP-7蛋白，（2）注射表达hBMP-7的关节软骨细胞的兔IVD外植体积累更多的蛋白多糖。基于这些发现，培训生提出使用离体基因转移方法研究BMP-7对退行性兔椎间盘的作用。她还进行了初步体内研究，并将同种异体兔关节软骨细胞移植到退化兔IVD中，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）担任了受训者的主要导师。她的体内研究也将得到D. Greg安德森，脊柱外科医生，具有丰富的动物椎间盘损伤模型经验。在修订后的培训计划中，受训人员提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一个丰富的环境，并有一个强有力的承诺，以支持她的职业发展。

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.