Abstract 3362: Serial MRI Evaluation of Stem Cell Efficacy Using Allogeneic, MR-labeled Stem Cells in a Rabbit Peripheral Arterial Disease Model: Comparison to X-ray Angiography and Histology
Introduction: Magnetic resonance (MR) angiography lacks the spatial resolution to detect angiogenesis. However, MR first-pass perfusion can offer a non-invasive method to determine the functional consequences of neovascularization. The purpose of the our study was to determine the efficacy of allogeneic mesenchymal stem cell (MSC) therapy in a randomized, placebo controlled trial in a rabbit peripheral arterial disease (PAD) model using non-invasive MRI.
Methods: Hindlimb ischemia was created by endovascular occlusion of the superficial femoral artery using platinum coils in female New Zealand White rabbits. At 24 hours post-occlusion, the rabbits were randomized to receive 13 million allogeneic ferumoxide-labeled MSCs (n = 8) or ferumoxide alone (n = 6) in 6 intramuscular injections to the medial adductor muscle. First pass saturation recovery perfusion MRIs (3T Philips Achieva) were obtained after a Gadomer injection (0.01 mmol/kg IV injection, Schering AG) prior to, 7, and 14 days post-IM injection. Signal-intensity time curves from MRI in the right and left calf were evaluated and compared to x-ray angiography on day 15 and histopathology (CD 31 staining for endothelial cells). A cross-section time series linear regression analysis with a P value <0.05 was considered statistically significant.
Results: At baseline, the difference in MR perfusion upslope time between ischemic (I) and non-ischemic (NI) limbs was worse in MSC-treated rabbits (5.0 ± 3 s) vs. controls (3.7 ± 3 s). X-ray angiography (TIMI frame count) showed improvement in both groups at 2 weeks. However, MRI perfusion in MSC rabbits showed more improvement (upslope time difference decreased 2.1 ± 1 s, P<0.04 vs. baseline) than controls (1.0 ± 1 s improvement, P=NS). Increased capillary density in the left limb relative to the right limb based on histopathology (28 ± 20 MSC vs.19 ± 22 control difference I vs. N, P=NS) was present in all animals except one control animal.
Conclusions: MRI offers a non-invasive means to serially determine tissue perfusion without arterial access that is in good agreement with angiographic and histopathologic gold standards for assessing response to cellular therapy in PAD. In this model, MSC therapy shows modest improvements in perfusion relative to controls.