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 T2 and T2*, 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.