TY - JOUR
T1 - Autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the diabetic mouse hindlimb
AU - Sica, Vincenzo
AU - Williams-Ignarro, Sharon
AU - De Nigris, Filomena
AU - D'Armiento, Francesco P.
AU - Lerman, Lilach O.
AU - Balestrieri, Maria Luisa
AU - Maione, Ciro
AU - Palagiano, Antonio
AU - Rossiello, Luigi
AU - Ignarro, Louis J.
AU - Napoli, Claudio
PY - 2006/12/15
Y1 - 2006/12/15
N2 - Peripheral arterial disease (PAD) is a major health problem especially when associated to diabetes. Administration of autologous bone marrow cells (BMC) is emerging as a novel intervention to induce therapeutic angiogenesis in experimental ischemic limb models and in patients with PAD. Since tissue ischemia and diabetes are associated with an overwhelming generation of oxygen radicals and detrimental effects due to formation of glycosylation end-products, metabolic intervention with antioxidants and L-arginine can confer beneficial effects beyond those achieved by BMC alone. The effects of cotreatment with intravenous BMCs and metabolic vascular protection (1.0% vitamin E, 0.05% vitamin C, and 6% L-arginine) were examined in the ischemic hindlimb of diabetic and non diabetic mice. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and decreased interstitial fibrosis. This effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation.
AB - Peripheral arterial disease (PAD) is a major health problem especially when associated to diabetes. Administration of autologous bone marrow cells (BMC) is emerging as a novel intervention to induce therapeutic angiogenesis in experimental ischemic limb models and in patients with PAD. Since tissue ischemia and diabetes are associated with an overwhelming generation of oxygen radicals and detrimental effects due to formation of glycosylation end-products, metabolic intervention with antioxidants and L-arginine can confer beneficial effects beyond those achieved by BMC alone. The effects of cotreatment with intravenous BMCs and metabolic vascular protection (1.0% vitamin E, 0.05% vitamin C, and 6% L-arginine) were examined in the ischemic hindlimb of diabetic and non diabetic mice. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and decreased interstitial fibrosis. This effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation.
KW - Bone marrow cell
KW - Diabetes
KW - Ischemic hindlimb
KW - L-arginine; antioxidants
KW - Nitric oxide
KW - Peripheral arterial disease
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U2 - 10.4161/cc.5.24.3568
DO - 10.4161/cc.5.24.3568
M3 - Article
C2 - 17172874
AN - SCOPUS:33845620251
SN - 1538-4101
VL - 5
SP - 2903
EP - 2908
JO - Cell Cycle
JF - Cell Cycle
IS - 24
ER -