Author: Toyama Y, Sasaki KI, Tachibana K, Ueno T, Kajimoto H, Yokoyama S, Ohtsuka M, Koiwaya H, Nakayoshi T, Mitsutake Y, Chibana H, Itaya N, Imaizumi T.
Department of Internal Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine.
Conference/Journal: Cardiovasc Res.
Date published: 2012 May 28
Other: Word Count: 173
AIMS: Unsatisfactory effects of therapeutic angiogenesis in critical limb ischemia may be ascribed to use of circulating angiogenic cells (CACs) with impaired neovascularization-related capacities of atherosclerotic patients. We tested whether ultrasound cell stimulation can restore the impaired capacities.Methods and ResultsDuring four-day-culture of human peripheral blood-derived mononuclear cells to achieve CACs, we stimulated the culture cells daily with low-intensity pulsed ultrasound stimulation (LIPUS). LIPUS to healthy volunteer-derived culture cells augmented generation and migration capacities of CACs, increased concentrations of angiopoietin 2 and nitrogen oxides in the culture medium, and increased expressions of phosphorylated-Akt and endothelial nitric oxide synthetase in CACs on western blotting. LIPUS to atherosclerotic patient-derived culture cells also augmented the generation and migration capacities of CACs. Although neovascularization in the ischemic hindlimb of athymic nude mice was impaired after intramuscular injection of atherosclerotic patient-derived CACs compared with that of healthy volunteer-derived CACs, LIPUS to atherosclerotic patient-derived culture cells restored the impaired neovascularization. CONCLUSION: Therapeutic angiogenesis with LIPUS-pretreated CACs may be a new strategy to rescue critical limb ischemia in atherosclerotic patients.