Development of an Autologous Macrophage-based Adoptive Gene Transfer Strategy to Treat Posttraumatic Osteoarthritis (PTOA) and Osteoarithritis (OA)
Technical Report,01 Sep 2013,28 Feb 2016
Loma Linda University Loma Linda United States
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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 TGF3 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.