Therapeutic angiogenesis for revascularization in peripheral artery disease

Abstract

Therapeutic angiogenesis for peripheral artery disease (PAD), achieved by gene and cell therapy, has recently raised a great deal of hope for patients who cannot undergo standard revascularizing treatment. Although pre-clinical studies gave very promising data, still clinical trials of gene therapy have not provided satisfactory results. On the other hand, cell therapy approach, despite several limitations, demonstrated more beneficial effects but initial clinical studies must be constantly validated by larger randomized, multi-center, double-blinded, placebo-controlled trials. This review focuses on previous and recent gene and cell therapy studies for limb ischemia, including both experimental and clinical research, and summarizes some important papers published in this field. Moreover, it provides a short comment on combined gene and cell therapy approach on the example of heme oxygenase-1 overexpressing cells with therapeutic properties.

Keywords: AdVEGF; Ang-1; BMDCs; BVR; Cell therapy; Del-1; EPCs; G-CSF; GM-CSF; GPx-1; Gene therapy; HGF; HIF-1α; HO-1; Heme oxygenase-1; IL-10; IL-1β; IL-6; Limb ischemia; MCP-1; MSCs; MnSOD; PAD; PBDCs; PDGF; Peripheral artery disease; PlGF; SDF-1; SnPP; TNFα; Therapeutic angiogenesis; VEGF; VEGF-R1; VEGF-R2; aFGF; acidic fibroblast growth factor; adenoviral vector encoding vascular endothelial growth factor; angiopoietin 1; bFGF; basic fibroblast growth factor; biliverdin reductase; bone marrow-derived cells; developmental endothelial locus-1; endothelial progenitor cells; glutathione peroxidase 1; granulocyte monocyte-colony stimulating factor; granulocyte-colony stimulating factor; heme oxygenase-1; hepatocyte growth factor; hypoxia inducible factor-1α; interleukin 1; interleukin 1β; interleukin 6; manganese superoxide dismutase; mesenchymal stem cells; monocyte chemotactic protein-1; peripheral artery disease; peripheral blood-derived cells; placental growth factor; platelet-derived growth factor; stromal cell-derived factor-1; tin protoporphyrin; tumor necrosis factor α; vWF; vascular endothelial growth factor; vascular endothelial growth factor receptor 1; vascular endothelial growth factor receptor 2; von Willebrand factor.