Noninvasive monitoring and tracking of muscle stem cell transplants.
BACKGROUND
Efficient techniques to noninvasively monitor stem cell transplants will accelerate the development of stem cell therapies. Magnetic resonance (MR) imaging of labeled stem cells is a noninvasive approach that can provide images with high spatial resolution. In this report, we have evaluated the ability of a commercially available, FDA-approved contrast agent to allow for the monitoring of therapeutic stem cell transplants in murine dystrophic muscle.


METHODS
Multipotent, muscle-derived stem cells were labeled by incubation with ferumoxide:polycation complexes. Labeled stem cells were evaluated for the ability to differentiate into mature myotubes and be detected by high resolution MR images in vitro and in vivo.


RESULTS
Endosomal accumulation of superparamagnetic iron-oxide resulted in changes in the MR contrast T(2) and T(2)*, allowing for three dimensional, noninvasive detection of labeled cells. Relaxivity measurements on cell phantoms indicate that less than eight labeled cells could be detected by MR imaging. Furthermore, therapeutic cellular grafts transplanted into dystrophic muscle could be imaged sequentially and these noninvasive images correlated with histological images obtained by conventional microscopy. Additional studies revealed that MR imaging is applicable to tracking the migration of a small number of labeled cells following arterial delivery.


CONCLUSIONS
MR monitoring is a highly sensitive technique that is applicable to muscle stem cell transplantation. We anticipate that it will enhance stem cell investigations by reducing the need for invasive tissue harvests and biopsies.
Cahill
Kevin S
KS
Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA.
Gaidosh
Gabriel
G
Huard
Johnny
J
Silver
Xeve
X
Byrne
Barry J
BJ
Walter
Glenn A
GA
D000818:Animals; D001158:Arteries / Q000166:cytology; D016923:Cell Death; D002454:Cell Differentiation; D002478:Cells, Cultured; D008279:Magnetic Resonance Imaging; D051379:Mice; D009132:Muscles / Q000166:cytology*; D009137:Muscular Dystrophy, Animal / Q000628:therapy*; D033581:Stem Cell Transplantation