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-[(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.


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 (2x10(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.
Zhang
Yan
Y
Division of Cardiac Surgery, University of Ottawa, Ottawa, Canada.
Thorn
Stephanie
S
DaSilva
Jean N
JN
Lamoureux
Marc
M
DeKemp
Robert A
RA
Beanlands
Rob S
RS
Ruel
Marc
M
Suuronen
Erik J
EJ
D000818:Animals; D002465:Cell Movement; D003094:Collagen; D019788:Fluorodeoxyglucose F18; D006614:Hindlimb; D006801:Humans; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D003094:Collagen