Fluorescence molecular tomography enables in vivo visualization and quantification of nonunion fracture repair induced by genetically engineered mesenchymal stem cells

Fluorescence molecular tomography (FMT) is a novel tomographic near‐infrared (NIR) imaging modality that enables 3D quantitative determination of fluorochrome distribution in tissues of live small animals at any depth. This study demonstrates a noninvasive, quantitative method of monitoring engineered bone remodeling via FMT. Murine mesenchymal stem cells overexpressing the osteogenic gene BMP2 (mMSCs‐BMP2) were implanted into the thigh muscle and into a radial nonunion bone defect model in C3H/HeN mice. Real‐time imaging of bone formation was performed following systemic administration of the fluorescent bisphosphonate imaging agent OsteoSense™, an hydroxyapatite‐directed bone‐imaging probe. The mice underwent imaging on days 7, 14, and 21 postimplantation. New bone formation at the implantation sites was quantified using micro‐computed tomography (micro‐CT) imaging. A higher fluorescent signal occurred at the site of the mMSC‐BMP2 implants than that found in controls. Micro‐CT imaging revealed a mass of mature bone formed in the implantation sites on day 21, a finding also confirmed by histology. These findings highlight the effectiveness of FMT as a functional platform for molecular imaging in the field of bone regeneration and tissue engineering. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:522–530, 2008