doi: 10.1161/CIRCIMAGING.108.781120
Original Articles |
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
From the Division of Cardiac Surgery (Y.Z., M.R., E.J.S.); Cardiac PET Centre, Division of Cardiology (Y.Z., S.T., J.N.D., M.L., R.A.d., R.S.B.); the Department of Cellular and Molecular Medicine (Y.Z., S.T., J.N.D., R.S.B., M.R., E.J.S.); and the Molecular Function and Imaging Program (all authors), University of Ottawa, Ottawa, Canada.
Correspondence to Erik J. Suuronen, PhD, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Canada K1Y 4W7. E-mail esuuronen{at}ottawaheart.ca or mruel@ottawaheart.ca
Received March 20, 2008; accepted September 19, 2008.
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-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) was used to label transplanted circulating progenitor cells (CPCs) and track them in vivo with positron-emission tomography.
Methods and Results— Efficiency of 18F-FDG cell labeling was CPC-concentration dependent (r=0.61, P<0.001) but not 18F-FDG-dose dependent. Labeled human CPCs (2x106) 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 18F-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 18F-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 18F-FDG labeled cells and positron-emission tomography imaging and confirmed by biodistribution and histology.
Key Words: stem cells • tissue engineering • transplantation • ischemia • imaging
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Circ Cardiovasc Imaging 2008 1: 197-204.[Abstract] [Full Text] [PDF]