title: Therapeutic angiogenesis for critical limb ischemia.
abstract: The application of gene- and cell-based therapies to promote angiogenesis is a novel concept to treat lower-limb critical limb ischemia (CLI) and may provide an unmet need for patients with no options for revascularization. Proof of concept was demonstrated in animal models resulting in clinical trials that have confirmed the feasibility and short-term efficacy of intramuscular injection of angiogenetic tissue growth factors or bone marrow stem cells. The safety of these biologic therapies has been demonstrated in randomized clinical trials with no "off-target" angiogenesis, growth of occult tumors, or progression of diabetic retinopathy. Current phase III randomized clinical trials using a DNA plasmid with the hepatocyte growth factor gene or bone marrow aspirate concentrate of mesenchymal cells are designed to address several crucial issues, including proper patient selection criteria, relevant clinical endpoints, and long-term efficacy. Because effectiveness of these novel therapies remains to be established, ongoing and future randomized clinical trials should be placebo-controlled, investigator-blinded, and have amputation-free survival as the primary endpoint. Further development of efficient gene transfer techniques and keeping transplanted stem cells healthy have the potential to make biologic therapies more robust in promoting angiogenesis, tissue regeneration, and resolution of CLI symptoms. If sustained efficacy can be demonstrated, new therapeutic strategies for patients with CLI will be available for clinicians, ie, limb revascularization using angiogenic gene or stem cell therapy alone, or in conjunction with endovascular intervention.
authors: Division of Vascular and Endovascular Surgery, University of California, San Diego, School of Medicine, Sulpizio Cardiovascular Center, 7404 Medical Center Drive, Mail Code 7403, La Jolla, CA 92037.
authors: Sae Hee
authors: SH
authors: Ko
authors: Division of Vascular and Endovascular Surgery, University of California, San Diego, School of Medicine, Sulpizio Cardiovascular Center, 7404 Medical Center Drive, Mail Code 7403, La Jolla, CA 92037. Electronic address: dbandyk@ucsd.edu.
authors: Dennis F
authors: DF
authors: Bandyk
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D003131:Combined Modality Therapy; D016638:Critical Illness; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007511:Ischemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D012039:Regional Blood Flow; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D042501:Angiogenic Proteins