Advances in Growth Factor Delivery for Therapeutic Angiogenesis

Abstract

Therapeutic angiogenesis is a new revascularization strategy involving the administration of growth factors to induce new vessel formation. The biology and delivery of angiogenic growth factors involved in vessel formation have been extensively studied but success in translating the angiogenic capacity of growth factors into benefits for vascular disease patients is still limited. This could be attributed to issues related to patient selection, growth factor delivery methods or lack of vessel maturation. Comprehensive understanding of the cellular and molecular cross-talk during the different stages of vascular development is needed for the design of efficient therapeutic strategies. The presentation of angiogenic factors either in series or in parallel using a strategy that mimics physiological events, such as concentration and spatio-temporal profiles, is an immediate requirement for functional blood vessel formation. This review provides an overview of the recent delivery strategies of angiogenic factors and discusses targeting neovascular maturation as a promising approach to induce stable and functional vessels for therapeutic angiogenesis.

R-Ras Inhibits VEGF-Induced p38MAPK Activation and HSP27 Phosphorylation in Endothelial Cells

“…The imbalanced signals due to excessive VEGF stimuli leads to overproduction of immature and defective vessels with chaotic organization as seen in pathological angiogenesis in tumors and diabetic retinopathy [6, 7]. In peripheral arterial disease, imbalanced angiogenesis appears to be a crucial reason for the failure of clinical trials for VEGF gene therapy that were conducted in attempts to reperfuse ischemic tissues with VEGF-induced new vessels [8–10]. …”

Collaterals: Implications in cerebral ischemic diseases and therapeutic interventions

“…On the other hand, angiogenesis, sprouting of new capillaries from postcapillary venules, is active during the chronic process of hypoxia and a driving force for post ischemic neovascularization. Although cell based therapeutic angiogenesis still holds promise for the treatment of ischemic diseases, delivering angiogenic factors in the form of protein or gene therapy has not resulted in clinical benefit (Chu and Wang, 2012, Said et al, 2013). Understanding the mechanisms underlying each remodeling process, regardless whether unique or shared, is the first step towards the development of effective revascularization therapy.…”

Lower-extremity arterial revascularization: Is there any evidence for diabetic foot ulcer-healing?

“…Based on preliminary conclusive data in animal models, different ways to stimulate angiogenesis through growth factors, gene therapy and progenitor cell administration have been investigated in patients with CLI [79]. However, human studies are often limited because they are not randomized and/or have small cohorts.…”