title: Autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the diabetic mouse hindlimb.
abstract: 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.
authors.affiliation: Department of General Pathology, Division of Clinical Pathology and Excellence Research Center on Cardiovascular Diseases, 1st School of Medicine, II University of Naples, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sica
authors.forename: Sharon
authors.initials: S
authors.lastname: Williams-Ignarro
authors.forename: Filomena
authors.initials: F
authors.lastname: de Nigris
authors.forename: Francesco P
authors.initials: FP
authors.lastname: D'Armiento
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Balestrieri
authors.forename: Ciro
authors.initials: C
authors.lastname: Maione
authors.forename: Antonio
authors.initials: A
authors.lastname: Palagiano
authors.forename: Luigi
authors.initials: L
authors.lastname: Rossiello
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Ignarro
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental; D005355:Fibrosis; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007249:Inflammation; D007511:Ischemia / Q000139:chemically induced / Q000503:physiopathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D009132:Muscles / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012039:Regional Blood Flow; D014182:Transplantation, Autologous
chemical_list: D019394:Ki-67 Antigen