Cellular and molecular therapeutic modalities for arterial obstructive syndromes.
Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), peripheral arterial disease (PAD), and cerebral vascular disease (CVD) is a major goal for modern medicine. Molecular and cell-based therapies for arterial obstructive syndromes have the potential to become clinically useful in the near future. Molecular therapy employs angiogenic proteins and genes in order to initiate the development of new blood vessels that by-pass an arterial occlusion. The induction of a collateral artery system is termed therapeutic angiogenesis or neovascularization. Proteins have been delivered either directly into the ischemic area or via a vector encoding an angiogenic gene. Both protein and gene therapies have been associated with promising preclinical and early phase human trial results in patients with PAD as well as CAD. However, to date, efficacy has not been demonstrated in placebo-controlled, large trails. Today's cell-based therapy is focused on stem cells (SCs) for the treatment of patients after acute myocardial infarction (AMI) or for patients with severe left ventricular dysfunction. Stem cells have shown to increase cardiac performance in uncontrolled, early phase human studies. This improvement is believed to have its origin in myogenesis and neovascularization. In the following review, we will cover current state of molecular- and cellular-based treatments for PAD and CAD that have reached the clinical arena.
Staudacher
Dawid L
DL
Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Bruce Rappaport School of Medicine, Technion-IIT, 7 Michal Street, Haifa 34362, Israel.
Preis
Meir
M
Lewis
Basil S
BS
Grossman
P Michael
PM
Flugelman
Moshe Y
MY
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000473:pathology / Q000628:therapy*; D003115:Colony-Stimulating Factors / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D003115:Colony-Stimulating Factors; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors