Abstract 17627: Perivascular Delivery of Microbead-Encapsulated Mesenchymal Stem Cells Improves Perfusion Recovery After Limb Ischemia
Objective: Stem cell therapy holds promise for the treatment of peripheral vascular disease. However, the optimal method for cell delivery to achieve maximum therapeutic effect, i.e. efficient collateralization, is still debated. We tested the feasibility and efficacy of perivascular application of mesenchymal stem cells (MSCs) as a novel method to bypass the artery blockage.
Methods and Results: Ten week-old CD1 mice underwent unilateral limb ischemia by femoral artery occlusion, followed by randomized treatment with vehicle (V), microbead-encapsulated MSCs (MB-MSCs) or microbeads alone (MB) injected in the perivascular space around the femoral artery and vein (n=12 in each group) at the site of vascular occlusion. Laser Doppler showed a marked improvement of blood flow recovery in the MB-MSCs group (P<0.001 vs. V or MB, from day 7 to 21 after ischemia). Final measurement of muscular blood flow by fluorescent microspheres confirmed the improvement in MB-MSCs group (0.960.06 vs. 0.820.02 ml/gm of tissue in V and vs. 0.850.01 ml/gm in MB, P<0.001). Histological analysis at day 21 revealed increased capillary (88015 vs. 67316/mm2in V and vs. 73512/mm2in MB) and arteriole density (150.5 vs. 100.4/mm2 in V and vs. 100.3/mm2 in MB, P<0.001 for both comparisons). Whole mount IHC demonstrated numerous functional capillaries and arterioles bridging the space between MB-MSCs and the ischemic muscles at the site of femoral artery occlusion (Figure). These effects were absent in the group treated with microbeads alone. Cytometry bead array and RT-PCR profiler analysis showed activation of genes regulating angiogenesis pathway in the MB-MSCs group.
Conclusion: We newly show the feasibility and efficacy of perivascular delivery of MSCs to enhance peri-occlusional collaterals and improve reperfusion following limb ischemia. This novel biological bypass method might be particularly useful in patients not amenable to conventional revascularization.
- © 2012 by American Heart Association, Inc.