Shao-Pow Lin MD, PhD, Presenter: Nothing to Disclose

Todd Meyerrose, Abstract Co-Author: Nothing to Disclose

Andrew Hope MD, Abstract Co-Author: Nothing to Disclose

The migration kinetics of transplanted hematologic stem cells (HSC) after introduction into the peripheral venous vasculature is largely unknown. Our goal was to demonstrate the feasibility of dynamically tracking these cells to target tissues with in vivo magnetic resonance imaging (MRI) during post-transplant homing and engraftment.

CELL PREPARATION & TRANSPLANTATION: Human umbilical cord blood-derived HSC were loaded with 0.9 μm polymer microspheres containing super-paramagnetic iron oxide (SPIO) and Dragon Green fluorescent dye. Positively-loaded cells were magnetically separated and transplanted into sub-lethally irradiated NOD/SCID/MPSVII knock-out mice via the retro-orbital venous sinus. IN VIVO MRI: Images of the spleen were acquired at 4.7 T with a quadrature detection coil. Multi-slice, susceptibility-sensitive, gradient echo imaging parameters were: TE = 6 ms, TR = 190 ms, FOV = 3.5 x 3.0 cm, Matrix = 128 x 128, and NEX = 16. After acquisition of a pre-transplant image, the mice were irradiated and the labeled HSC injected. Subsequently, each animal (n=2) was imaged for 12 hours post-transplantation. EX VIVO ANALYSIS: Post-transplant analysis of human (transplanted) HSC content within the excised mouse spleens was determined by flow cytometry with verification by histologic examination and quantitation with quantitative PCR.

Analysis of excised spleens demonstrated the accumulation of HSC over the first 12 hours post-transplant, with a subsequent emigration of cells away from the spleen, presumably to secondary sites as yet unidentified. In vivo, longitudinal, gradient echo imaging during the initial phase of cellular homing demonstrated a progressive loss of MR signal intensity. At 12 hours, the signal intensity decreased by 29% relative to the pre-transplant intensity. In contrast, repetitive imaging of a non-transplanted mouse demonstrated signal variability of only +/- 4% from the mean.

The dynamic accumulation of SPIO-labeled HSC can be detected in vivo with gradient echo MR imaging. This method has potential applications in both the in vivo study of cellular homing and the clinical evaluation of stem cell-based therapies.

Lin, S, Meyerrose, T, Hope, A, In Vivo Tracking of Stem Cell Migration with Magnetic Resonance Imaging.  Radiological Society of North America 2005 Scientific Assembly and Annual Meeting, November 27 - December 2, 2005 ,Chicago IL. http://archive.rsna.org/2005/4409020.html