Abstract 16828: Human Neural Stem Cell Line Promotes Neovascularization and Accelerates Perfusion Recovery in a Diabetic Mouse Model of Limb Ischemia
Objective: CTX0E03 is a renewable and stable human neural stem cell line currently approved for a clinical trial on patients with ischemic stroke. The objective of this preclinical study was to examine the therapeutic value of CTX0E03 cells in a model of limb ischemia.
Methods: In vitro angiogenesis activity of CTX0E03 was verified using the AngioKit assay (TCS CellWorks). Cell therapy with CTX0E03 (intramuscular injection of 3X104, 3X105 or 1.5X106 or vehicle) was applied to streptozotocin-induced diabetic mice upon unilateral limb ischemia induction (n=10 per group). A similar protocol was applied in non-diabetic mice. Main endpoints were: (1) number of necrotic toes, (2) superficial blood flow (BF, laser Doppler), (3) adductor muscle BF (florescent microspheres), (4) pO2 (Oxford Optronics), (5) capillary and arteriole density (immunohistochemistry) and (6) persistence of CTX0E03 cells at 21d post-injection.
Results: CTX0E03 cells increased total tube formation compared with vehicle in the AngioKit assay. Vehicle-treated diabetic mice showed an impaired BF recovery compared to non-diabetic mice, due to reduced reparative neovascularization. The two higher doses of CTX0E03 reduced toe necrosis and markedly improved laser Doppler BF recovery (Figure A) and adductor muscle BF, pO2, and capillary and arteriole density in diabetic (P<0.05 vs vehicle for all comparisons, Figure B) and non-diabetic mice (data not shown). CTX0E03 cells could not be detected in injected muscles at 21d, suggesting early support of neovascularization by CTX0E03 to be the mechanism of durable healing.
Conclusions: CTX0E03 cell therapy improves clinically relevant aspects of limb ischemia in a diabetic mouse model in a dose dependent manner by enhancing neovascularization. This study is the first to demonstrate the healing action of human neuronal stem cells in peripheral ischemia.
- © 2010 by American Heart Association, Inc.