Circulation. 2003;108:1009-1014
Published online before print August 11, 2003, doi: 10.1161/01.CIR.0000084537.66419.7A
Published online before print August 11, 2003, doi: 10.1161/01.CIR.0000084537.66419.7A
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(Circulation. 2003;108:1009.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Serial Cardiac Magnetic Resonance Imaging of Injected Mesenchymal Stem Cells
From the Cardiovascular Branch (J.M.H., A.J.D., V.K.R., B.S.S.P., R.J.L.), Laboratory of Cardiac Energetics (R.B.T., E.R.M.), Pathology Branch (Z.-X.Y.), and Hematology Branch (K.A.H., C.E.D.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, and Osiris Therapeutics (T.R.V., B.K.M.), Baltimore, Md.
Correspondence to Robert J. Lederman, MD, Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 2c713, Bethesda, MD 20892-1538. E-mail lederman{at}nih.gov
Received November 18, 2002; de novo received February 25, 2003; revision received April 29, 2003; accepted May 2, 2003.
Background— Delivery and tracking of endomyocardial stem cells are limited by the inability to image transplanted cells noninvasively in the beating heart. We hypothesized that mesenchymal stem cells (MSCs) could be labeled with a iron fluorophore particle (IFP) to provide MRI contrast in vivo to assess immediate and long-term localization.
Methods and Results— MSCs were isolated from swine. Short-term incubation of MSCs with IFP resulted in dose-dependent and efficient labeling. Labeled cells remained viable for multiple passages and retained in vitro proliferation and differentiation capacity. Labeled MSCs (104 to 106 cells/150 µL) were injected percutaneously into normal and freshly infarcted myocardium in swine. One, 3, and 1 animals underwent serial cardiac MRI (1.5T) for 4, 8, and 21 days, respectively. MRI contrast properties were measured both in vivo and in vitro for cells embedded in agar. Injection sites containing as few as 105 MSCs could be detected and contained intact IFP-bearing MSCs on histology.
Conclusions— IFP labeling of MSCs imparts useful MRI contrast, enabling ready detection in the beating heart on a conventional cardiac MR scanner after transplantation into normal and infarcted myocardium. The dual-labeled MSCs can be identified at locations corresponding to injection sites, both ex vivo using fluorescence microscopy and in vivo using susceptibility contrast on MRI. This technology may permit effective in vivo study of stem cell retention, engraftment, and migration.
Key Words: cells • magnetic resonance imaging • myocardial infarction • contrast media
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