Cell Therapy for the degenerating intervertebral discs

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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.