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

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

Fingerprint

Glypicans
Fibroblast Growth Factor 2
Intercellular Signaling Peptides and Proteins
Medical problems
Angiogenesis Inducing Agents
Tissue
Therapeutics
Ischemia
Extremities
Alginate
Endothelial cells
Blood vessels
Cell proliferation
Cell- and Tissue-Based Therapy
Skin
Vascular Diseases
Type 2 Diabetes Mellitus
Cell Movement
Blood Vessels
Endothelial Cells

Keywords

  • growth factor
  • angiogenesis
  • vascular disease

Cite this

Monteforte, Anthony J. ; Lam, Brian ; Das, Subhamoy ; Mukhopadhyay, Somshuvra ; Wright, Catherine S. ; Martin, Patricia E. ; Dunn, Andrew K. ; Baker, Aaron B. / Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis. In: Biomaterials. 2016 ; Vol. 94. pp. 45-56.
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Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis. / Monteforte, Anthony J.; Lam, Brian; Das, Subhamoy; Mukhopadhyay, Somshuvra; Wright, Catherine S.; Martin, Patricia E.; Dunn, Andrew K.; Baker, Aaron B.

In: Biomaterials, Vol. 94, 07.2016, p. 45-56.

Research output: Contribution to journalArticle

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T1 - Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis

AU - Monteforte, Anthony J.

AU - Lam, Brian

AU - Das, Subhamoy

AU - Mukhopadhyay, Somshuvra

AU - Wright, Catherine S.

AU - Martin, Patricia E.

AU - Dunn, Andrew K.

AU - Baker, Aaron B.

N1 - Accepted 30-3-16 (email in SAN) Online pub 11-4-16

PY - 2016/7

Y1 - 2016/7

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