Abstract 15690: Longitudinal in vivo Assessment of Bone Marrow Mononuclear Cell Therapy for Ischemia-Mediated Neovascularization
Background: There is strong interest in bone marrow-derived mononuclear cells (BM-MNCs) for therapeutic enhancement of ischemia-mediated neovascularization. However, clinical trials to date have yielded contradictory results. We hypothesize that varying cell number and delivery routes may contribute to these inconsistencies. Using bioluminescent imaging we longitudinally evaluate the effects of cell number and delivery route on therapeutic efficacy, homing, survival and engraftment of BM-MNCs in a murine model of hindlimb ischemia.
Methods and Results: The contribution of BM-MNCs in ischemia-mediated neovascularization was assessed via intramuscular (IM) or intravenous (IV) transplantation of BM-MNCs (2x105/1x106) that were extracted from the bone marrow of transgenic FVB-L2G mice (ubiquitously expressing Fluc and GFP reporter genes) and injected into syngeneic FVB/N mice after surgery (n=5-6/group). Recovery was monitored with Laser Doppler Perfusion Imaging. IM treatments of 1x106 cells increased reperfusion compared to controls with p<0.001 on Days 4 (0.56±0.06 v 0.25±0.04) and 7 (0.88±0.07 v 0.57±0.13). Similarly, IV treatments of 1x106 cells increased reperfusion on Days 7 (p< 0.01, 0.74±0.09 v 0.54±0.09) and 14 (p<0.05, 0.87±0.03 v 0.73±0.09). The 1x106 IM treatments when compared to IV were superior for accelerating reperfusion (Day 4, p<0.01, 0.56±0.06 v 0.26±0.02). Bioluminescent imaging after tail-vein IV showed aggregation of cells in the lungs and spleen prior to dispersion, with peak homing to ischaemic sites on Day 14 (p<0.001 v control) before trending back towards baseline. At 6 weeks, anti-GFP staining in tissue showed some cell engraftment colocalizing with CD31+ stains. Injections of 2x105 cells showed no increased recovery.
Conclusion: Both delivery routes of 1x106 BM-MNCs improved recovery and showed engraftment at vasculature. Despite IV injections homing to ischemic sites, IM delivery had greater therapeutic effect.
- © 2013 by American Heart Association, Inc.