Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells.
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.


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 (10(4) to 10(6) cells/150 microL) 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 10(5) 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.
Hill
Jonathan M
JM
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 2c713, Bethesda, MD 20892-1538, USA.
Dick
Alexander J
AJ
Raman
Venkatesh K
VK
Thompson
Richard B
RB
Yu
Zu-Xi
ZX
Hinds
K Allison
KA
Pessanha
Breno S S
BS
Guttman
Michael A
MA
Varney
Timothy R
TR
Martin
Bradley J
BJ
Dunbar
Cynthia E
CE
McVeigh
Elliot R
ER
Lederman
Robert J
RJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008648:Mesoderm / Q000166:cytology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013552:Swine; D013556:Swine, Miniature
D003287:Contrast Media; D005456:Fluorescent Dyes; D007501:Iron