Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis

Anthony J. Monteforte, Brian Lam, Subhamoy Das, Somshuvra Mukhopadhyay, Catherine S. Wright, Patricia E. Martin, Andrew K. Dunn, Aaron B. Baker*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these treatments often have long term disease states and co-morbidities, such as diabetes and obesity, that make them resistant to angiogenic stimuli. In this study, we identified that human patients with type 2 diabetes have reduced levels of glypican-1 in the blood vessels of their skin. The lack of this key co-receptor in the tissue may make the application of exogenous angiogenic growth factors or cell therapies ineffective. We created a novel therapeutic enhancer for growth factor activity consisting of glypican-1 delivered in a nanoliposomal carrier (a "glypisome"). Here, we demonstrate that glypisomes enhance FGF-2 mediated endothelial cell proliferation, migration and tube formation. In addition, glypisomes enhance FGF-2 trafficking by increasing both uptake and endosomal processing. We encapsulated FGF-2 or FGF-2 with glypisomes in alginate beads and used these to deliver localized growth factor therapy in a murine hind limb ischemia model. Co-delivery of glypisomes with FGF-2 markedly increased the recovery of perfusion and vessel formation in ischemic hind limbs of wild type and diabetic mice in comparison to mice treated with FGF-2 alone. Together, our findings support that glypisomes are effective means for enhancing growth factor activity and may improve the response to local angiogenic growth factor therapies for ischemia.
Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalBiomaterials
Volume94
Early online date11 Apr 2016
DOIs
Publication statusPublished - Jul 2016

Keywords

  • growth factor
  • angiogenesis
  • vascular disease

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