Autologous Bone Marrow Cell Therapy and Metabolic Intervention in Ischemia-Induced Angiogenesis in the Diabetic Mouse Hindlimb

Vincenzo Sica, Sharon Williams-Ignarro, Filomena de Nigris, Francesco P. D’Armiento, Lilach O. Lerman, Maria Luisa Balestrieri, Ciro Maione, Antonio Palagiano, Luigi Rossiello, Louis Ignarro and Claudio Napoli

volume 5 | issue 24

15 december 2006
Pages: 2903 - 2908

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

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.