Collagen-Based Matrices Improve the Delivery of Transplanted Circulating Progenitor Cells

Abstract

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-[ 18 F]fluoro-2-deoxy- d -glucose ( 18 F-FDG) was used to label transplanted circulating progenitor cells (CPCs) and track them in vivo with positron-emission tomography. Methods and Results— Efficiency of 18 F-FDG cell labeling was CPC-concentration dependent ( r =0.61, P <0.001) but not 18 F-FDG-dose dependent. Labeled human CPCs (2�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 18 F-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 18 F-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 18 F-FDG labeled cells and positron-emission tomography imaging and confirmed by biodistribution and histology.