Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb

Claudio Napoli, Sharon Williams-Ignarro, Filomena De Nigris, Gaetano De Rosa, Lilach O. Lerman, Bartolomeo Farzati, Angelo Matarazzo, Giacomo Sica, Chiara Botti, Andrea Fiore, Russell E. Byrns, Daigo Sumi, Vincenzo Sica, Louis J. Ignarro

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Lower-limb ischemia is a major health problem. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include the intramuscular use of autologous bone marrow cells (BMCs). Because tissue ischemia is associated with an overwhelming generation of oxygen radicals and negative effects due to perturbed shear-stress, metabolic intervention with antioxidants and L-arginine could potentially induce beneficial effects beyond those achieved by BMCs. The protective effect of autologous BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% L-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute peripheral arterial occlusion, i.v. BMC therapy improved blood flow and increased capillary densities and expression of Ki-67, a proliferation- associated protein. This beneficial 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. Therefore, although a cautious approach is mandatory when experimental findings are extended to human diseases, autologous BMCs together with metabolic intervention could be an effective clinical treatment for peripheral arterial disease.

Original languageEnglish (US)
Pages (from-to)17202-17206
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
StatePublished - Nov 22 2005

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Keywords

  • Antioxidants
  • Ischemic hindlimb
  • L-arginine
  • Nitric oxide
  • Peripheral arterial disease

ASJC Scopus subject areas

  • General

Cite this

Napoli, C., Williams-Ignarro, S., De Nigris, F., De Rosa, G., Lerman, L. O., Farzati, B., Matarazzo, A., Sica, G., Botti, C., Fiore, A., Byrns, R. E., Sumi, D., Sica, V., & Ignarro, L. J. (2005). Beneficial effects of concurrent autologous bone marrow cell therapy and metabolic intervention in ischemia-induced angiogenesis in the mouse hindlimb. Proceedings of the National Academy of Sciences of the United States of America, 102(47), 17202-17206. https://doi.org/10.1073/pnas.0508534102