A triple fusion reporter gene system with bone or cartilage specific promoters will be used in cell-based tissue engineered constructs to perform non-invasive and real-time imaging of synthetic activities (differentiation &proliferation) of implanted cells for optimizing cartilage repair/regeneration. We currently have a NIAMS-funded P01 entitled """"""""Tissue Engineered Cartilage Repair"""""""" (P01), which is to use state-of-the-art tissue engineering to address issues of articular cartilage repair. NIAMS is offering this BIRT opportunity to supplement existing awards such as our P01, and one of the specific areas to be considered for support to establish new interdisciplinary collaboration is """"""""Soft Tissue Biology - Imaging Technologies"""""""". During past few years, we have made great strides in molecular imaging of stem cell transplants and implants. We are now well positioned to propose novel and specific imaging techniques that add value to the P01 by enabling non-invasive, real-time and quantitative monitoring of molecular events associated with stem cell and/or chondrocyte based cartilage repair and regeneration such as the expression of marker genes Col I, Col II, Col X, etc., to enhance all existing Projects as well as the research components within the existing Cores. Currently, all experimental read-outs or end-point analyses in the P01 are based on immuno-histochemistry, quantitative histomorphometry, and biomechanical tests. While all these are considered the """"""""gold standards"""""""" for outcome measures, a non-destructive (for in vitro experiments) and non-invasive (for in vivo animal studies), longitudinal, and quantitative means for tracking key events during cartilage repair down to the molecular level is much needed and currently unavailable. Our long-term goal is to create a Molecular Imaging Core that will be integrated into the existing P01. The major impact that this BIRT project will bring into the parent grant (P01) is to connect in vivo/ex vivo experiments with in vivo animal studies. Molecular imaging techniques proposed here will provide the kind of data at molecular and cellular level not seen before, which will not only aid the investigation of stem cell-based cartilage repair, but also add to our knowledge of soft tissue biology.
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