Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells Development and Demonstration by Ex Vivo Radionuclide Cell Labeling and In Vivo Tracking With Positron-Emission Tomography

Background-Collagen delivery matrices have been reported to improve the results of cell therapy, but knowledge of their mechanisms of action is limited. To evaluate whether a collagen matrix improves early engraftment posttransplantation, 2-[F-18]fluoro-2-deoxy-D-glucose (F-18-FDG) was used to label transplanted circulating progenitor cells (CPCs) and track them in vivo with positron-emission tomography. Methods and Results-Efficiency of F-18-FDG cell labeling was CPC-concentration dependent (r=0.61, P < 0.001) but not F-18-FDG-dose dependent. Labeled human CPCs (2 x 10(6)) were injected with or without a collagen-based matrix in the ischemic hind limb of rats (n = 12 per group) 2 weeks after femoral artery ligation. Imaging of labeled cells, acquired by small animal positron-emission tomography at 150 minutes postinjection, revealed greater CPC retention in the ischemic hind limb and less nonspecific leakage to other tissues (retention ratio, 0.44 +/- 0.08) when CPCs were delivered within the matrix, compared with cells injected alone (0.22 +/- 0.13, P=0.040) and with F-18-FDG injected with or without the matrix (0.10 +/- 0.05 and 0.11 +/- 0.05, respectively, P < 0.005). Tissue radionuclide biodistribution was performed after completion of positron-emission tomography imaging. When F-18-FDG-labeled cells were injected with the collagen matrix, accumulation was significantly increased (by 69.6%, P=0.021) in the target ischemic hind limb muscle and significantly reduced (by 14.8% to 31.4%, P < 0.05) in nonspecific tissues, compared with cells injected alone. Histology confirmed the increased retention in target tissue associated with the matrix. Conclusions-Early posttransplantation, a collagen matrix enhances progenitor cell retention and limits distribution to nonspecific tissues, as measured by the use of F-18-FDG labeled cells and positron-emission tomography imaging and confirmed by biodistribution and histology. (Circ Cardiovasc Imaging. 2008;1:197-204.)