Gene electrotransfer for Ischemic tissue

Abstract

Angiogenesis, vasculogenesis, and arteriogenesis are endogenous responses to obstructive arterial disease or trauma causing tissue ischemia such as atherosclerotic plaques obstructing perfusion of the lower limbs or myocardial ischemia. Sufficient growth of collateral vessels is often impaired in patients due to factors such as the underlying atherosclerosis, age, or diabetes. There are many preclinical and clinical studies seeking exogenous angiogenesis induction to alleviate tissue ischemia. Translation of these therapies into clinical applications could address a multitude of ailments including wound healing, tissue grafting, bone and muscle regeneration, and myocardial repair. Gene therapy approaches delivering angiogenic factors have been attempted using various gene delivery methods. This chapter will focus on evaluating preclinical studies investigating application of gene electrotransfer approaches for ischemic tissues, in particular for wound healing, peripheral artery disease, and myocardial infarction. Gene electrotransfer has been utilized to deliver proangiogenic factors such as vascular endothelial growth factor, insulin-like growth factor, basic fibroblast growth factor, angiopoietin, etc. Delivery and expression have been demonstrated minimally invasively and invasively to the skin, to skeletal muscle, and to cardiac muscle. Notable improvement in tissue perfusion was consistently reported in skin flap wound healing models, in hind limb ischemia models, and in cardiac muscle ischemia model.