Development of an Autologous Macrophage-based Adoptive Gene Transfer Strategy to Treat Posttraumatic Osteoarthritis (PTOA) and Osteoarithritis (OA)
Annual rept. 1 Sep 2013-31 Aug 2014
LOMA LINDA UNIV CA
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OA is the most common degenerative joint disease, and 12 of all OA are resulted from an acute trauma to the joint and are referred to as PTOA. There is no cure for PTOA or OA. This Discovery Award project seeks to obtain proof-of-concept type of evidence for the feasibility of and efficacy for an innovative autologous macrophage-based anti-catabolic and pro-chondrogenic combination adoptive gene therapy for treatment of PTOA. The rationale for the use of macrophages as the cell vehicle for targeted delivery and confined expression of the transgenes is based on definitive evidence that a PTOA development is associated with both acute and chronic inflammation of the synovium and b synovial inflammation triggers massive infiltration of activated macrophages. The idea of the combination macrophage-based adoptive gene therapy with both an anti-catabolic gene IL-1ra or IL-1 shRNA and a pro-chondrogenic gene TGF 3 is based on the assumption that comprehensive treatment of a disease with complex pathophysiology, such as PTOA, will require concerted treatments at multiple phases of the diseases. The proposed study will test two hypotheses 1 the autologous macrophage-based adoptive gene transfer strategy can effectively deliver and confine expression of an anti-catabolic gene IL-1ra or IL-1 shRNA along with a chondrogenic gene TGF 3 in the inflamed areas within the synovium of the PTOA joint and 2 the IL-1ra or IL-1 shRNA and TGF 3 combination autologous macrophage-based adoptive gene transfer strategy will reduce PTOA symptoms and promote articular cartilage regeneration in a mouse PTOA model.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research